Trial Outcomes & Findings for A Study of Retreatment With MabThera (Rituximab) in Combination With Methotrexate in Patients With Rheumatoid Arthritis (RA) (NCT NCT00422383)

NCT ID: NCT00422383

Last Updated: 2015-05-04

Results Overview

ACR20 defined as overall score of ≥20 in ACR number (ACRn) calculation. Overall score defined as lowest percent improvement from baseline (BL) of following 3 measures: tender joint count (TJC; 68 joints), swollen joint count (SJC: 66 joints), and the 3rd lowest improvement achieved by at least 3 of 5 remaining ACR core parameters: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain (visual analog assessment \[VAS\]), Health Assessment Questionnaire (HAQ), and C-Reactive Protein (CRP). If CRP missing, erythrocyte sedimentation rate (ESR) was used. In order for improvements in the ACRn score to be expressed as a positive result, rather than the negative changes that improvements represent, the final ACRn results were multiplied by negative 1. Last observation carried forward (LOCF) for TJC/SJC, HAQ, CRP/ESR, VAS. If change in CRP incalculable, change in ESR used. ACR20 set to Non-Responder if ACRn missing

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 378 participants
• Primary outcome timeframe: Week 48
• Results posted on: 2015-05-04

Participant Flow

Participant milestones

Measure	Rituximab Low Dose Plus (+) Methotrexate Participants received rituximab, 0.5 grams (g), intravenously (IV), on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 milligrams (mg), IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 milligrams per milliliter (mg/mL), orally (PO) or parenterally, as prescribed. Participants also received a stable dose of folate greater than or equal to (≥) 5 milligrams per week (mg/week) given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Overall Study STARTED	134	120	93	6	25
Overall Study COMPLETED	119	106	89	4	22
Overall Study NOT COMPLETED	15	14	4	2	3

Reasons for withdrawal

Measure	Rituximab Low Dose Plus (+) Methotrexate Participants received rituximab, 0.5 grams (g), intravenously (IV), on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 milligrams (mg), IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 milligrams per milliliter (mg/mL), orally (PO) or parenterally, as prescribed. Participants also received a stable dose of folate greater than or equal to (≥) 5 milligrams per week (mg/week) given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Overall Study Adverse Event	5	3	1	1	0
Overall Study Lack of Efficacy	4	4	2	1	1
Overall Study Lost to Follow-up	0	1	0	0	1
Overall Study Protocol Violation	1	1	1	0	0
Overall Study Withdrawal by Subject	5	5	0	0	1

Baseline Characteristics

A Study of Retreatment With MabThera (Rituximab) in Combination With Methotrexate in Patients With Rheumatoid Arthritis (RA)

Baseline characteristics by cohort

Measure	Rituximab Low Dose + Methotrexate n=134 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=119 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=93 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate n=6 Participants Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate n=25 Participants Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Total n=377 Participants Total of all reporting groups
Age, Continuous	53.58 years STANDARD_DEVIATION 12.805 • n=5 Participants	52.32 years STANDARD_DEVIATION 12.115 • n=7 Participants	51.26 years STANDARD_DEVIATION 12.179 • n=5 Participants	51.83 years STANDARD_DEVIATION 6.274 • n=4 Participants	52.32 years STANDARD_DEVIATION 8.882 • n=21 Participants	52.48 years STANDARD_DEVIATION 12.10 • n=8 Participants
Sex: Female, Male Female	110 Participants n=5 Participants	90 Participants n=7 Participants	77 Participants n=5 Participants	4 Participants n=4 Participants	16 Participants n=21 Participants	297 Participants n=8 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	29 Participants n=7 Participants	16 Participants n=5 Participants	2 Participants n=4 Participants	9 Participants n=21 Participants	80 Participants n=8 Participants

PRIMARY outcome

Timeframe: Week 48

Population: ITT-M2 population

ACR20 defined as overall score of ≥20 in ACR number (ACRn) calculation. Overall score defined as lowest percent improvement from baseline (BL) of following 3 measures: tender joint count (TJC; 68 joints), swollen joint count (SJC: 66 joints), and the 3rd lowest improvement achieved by at least 3 of 5 remaining ACR core parameters: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain (visual analog assessment [VAS]), Health Assessment Questionnaire (HAQ), and C-Reactive Protein (CRP). If CRP missing, erythrocyte sedimentation rate (ESR) was used. In order for improvements in the ACRn score to be expressed as a positive result, rather than the negative changes that improvements represent, the final ACRn results were multiplied by negative 1. Last observation carried forward (LOCF) for TJC/SJC, HAQ, CRP/ESR, VAS. If change in CRP incalculable, change in ESR used. ACR20 set to Non-Responder if ACRn missing

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=134 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=119 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=93 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Percentage of Participants With a Response as Determined by American College of Rheumatology (ACR) 20% Improvement (ACR20)	64.2 percentage of participants Interval 56.0 to 72.0	63.9 percentage of participants Interval 55.0 to 72.0	72.0 percentage of participants Interval 63.0 to 81.0	—	—

SECONDARY outcome

Timeframe: Week 48

Population: ITT-M2 population

ACR50 was defined as an overall score of 50 in the ACRn calculation. Overall score defined as lowest percent improvement from BL of following 3 measures: TJC (68 joints), SJC (66 joints), and the 3rd lowest improvement achieved by at least 3 of 5 remaining ACR core parameters: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain (VAS), HAQ, and CRP. If CRP missing, ESR was used. In order for improvements in the ACRn score to be expressed as a positive result, rather than the negative changes that improvements represent, the final ACRn results were multiplied by negative 1. LOCF for TJC/SJC, HAQ, CRP/ESR, VAS. If change in CRP incalculable, change in ESR used. ACR50 set to Non-Responder if ACRn missing.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=134 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=119 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=93 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Percentage of Participants With ACR 50% Improvement Criteria (ACR50) Response at Week 48	39 percentage of participants	39 percentage of participants	48 percentage of participants	—	—

SECONDARY outcome

Timeframe: Week 48

Population: ITT-M2 population

ACR70 was defined as an overall score of 70 in the ACRn calculation. The Overall score defined as lowest percent improvement from BL of following 3 measures: TJC (68 joints), SJC (66 joints), and the 3rd lowest improvement achieved by at least 3 of 5 remaining ACR core parameters: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain (VAS), HAQ, and CRP. If CRP missing, ESR was used. In order for improvements in the ACRn score to be expressed as a positive result, rather than the negative changes that improvements represent, the final ACRn results were multiplied by negative 1. LOCF for TJC/SJC, HAQ, CRP/ESR, VAS. If change in CRP incalculable, change in ESR used. ACR70 set to Non-Responder if ACRn missing.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=134 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=119 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=93 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Percentage of Participants With a ACR 70% Improvement Criteria (ACR70) Response at Week 48	20 percentage of participants	19 percentage of participants	23 percentage of participants	—	—

SECONDARY outcome

Timeframe: BL, Week 48

Population: ITT-M2 population. Two participants from the Low Dose group and 1 participant from the Escalated Dose group were not evaluated for this outcome measure.

DAS28 was calculated according to the following formula: DAS28 equals (=) [0.56 multiplied by (*) the square root (√) of TJC] plus (+) [0.28 * √ of SJC] + (0.70 * the natural logarithm (ln) ESR in millimeters per hour (mm/h)] + [0.014 * participant's global assessment of disease activity (GH)]. DAS28-ESR ≥ 5.1 = high disease activity, DAS28-ESR less than or equal to (≤) 3.2 = low disease activity, DAS28-ESR less than (<) 2.6 = remission.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=132 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=118 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=93 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR): Adjusted Mean Change From BL at Week 48	-2.13 score on a scale Interval -2.38 to -1.87	-2.19 score on a scale Interval -2.45 to -1.92	-2.42 score on a scale Interval -2.71 to -2.12	—	—

SECONDARY outcome

Timeframe: Week 48

Population: ITT-M2 population

EULAR responses were categorized according to DAS28-ESR score. DAS28-ESR ≤ 3.2 at Week 48 and a change from BL to Week 48 < -1.2 = good response, DAS28-ESR ≤ 3.2 or greater than (>) 3.2 and ≤ 5.1 at Week 48 and a change from BL to Week 48 < -0.6 and ≥ -1.2 = moderate response, DAS28-ESR > 3.2 and ≤ 5.1 at Week 48 and a change from BL to Week 48 < -1.2 = moderate response, DAS28-ESR > 5.1 at Week 48 and a change from BL to Week 48 < -1.2 = moderate response, DAS28-ESR ≤ 3.2 or > 3.2 and ≤ 5.1 at Week 48 and a change from BL to Week 48 ≥ -0.6 = no response, DAS28-ESR > 5.1 at Week 48 and a change from BL to Week 48 < -0.6 and ≥ -1.2 or ≥ -0.6 = no response.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=134 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=119 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=93 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Percentage of Participants With a Response at Week 48 by European League Against Rheumatism (EULAR) Category None	26.9 percentage of participants	27.7 percentage of participants	10.8 percentage of participants	—	—
Percentage of Participants With a Response at Week 48 by European League Against Rheumatism (EULAR) Category Moderate	50.7 percentage of participants	55.5 percentage of participants	62.4 percentage of participants	—	—
Percentage of Participants With a Response at Week 48 by European League Against Rheumatism (EULAR) Category Good	22.4 percentage of participants	16.8 percentage of participants	26.9 percentage of participants	—	—

SECONDARY outcome

Timeframe: BL, Week 48

Population: ITT-M2 population. 9, 4, 2, and 1 participants were not evaluated for this outcome measure from the Low Dose, Escalated Dose, High Dose, and Decreased Dose groups, respectively.

FACIT-F scores were obtained from a 13 question self-administered participant questionnaire designed to measure the degree of fatigue experienced by participants in the previous 7 days. Participants responded to the questions using a value between 0 and 4, where 0 indicated "not at all" and 4 indicated "very much." 11 of the 13 questions were negatively stated; indicating the higher the score of the participant's response, the greater their fatigue. These questions were calculated as 4 minus the participants' response, so that a higher score indicated an improvement in health. The scores for the 2 positively stated questions were not changed. The participants' responses were summed to result in an overall score, which are scored 0 to 52 (52 = highest level of functioning). A positive change from BL indicated improvement.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=125 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=115 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=91 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate n=6 Participants Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate n=24 Participants Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score From BL at Week 48	6.605 score on a scale Standard Deviation 10.1529	8.109 score on a scale Standard Deviation 10.2876	8.364 score on a scale Standard Deviation 9.8368	2.000 score on a scale Standard Deviation 16.0250	6.192 score on a scale Standard Deviation 12.0081

SECONDARY outcome

Timeframe: BL, Week (Wk) 24 and 48

Population: ITT-M2 population, n (number) = number of participants analyzed for the given parameter at the specified timepoint.

SF-36 scores were obtained by scoring participants' responses to a 36 item questionnaire. SF-36 evaluated 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health from a range of 1 (better) to 5 (worst). The score for each section was an average of the individual question scores, which were scaled 0-100 (100=highest level of functioning). These 8 aspects were summarized as physical and mental component scores.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=128 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=116 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=91 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Short-Form 36 Health Survey (SF-36) Score Physical Role Score: Wk 24 (n=117,109,86)	37.694 score on a scale Standard Deviation 9.8439	36.977 score on a scale Standard Deviation 9.6325	39.027 score on a scale Standard Deviation 10.9050	—	—
Short-Form 36 Health Survey (SF-36) Score Physical Role Score: Wk 48 (n=119,102,89)	38.599 score on a scale Standard Deviation 10.9559	39.086 score on a scale Standard Deviation 9.6230	40.362 score on a scale Standard Deviation 10.1419	—	—
Short-Form 36 Health Survey (SF-36) Score Bodily Pain Score: BL (n=128,115,90)	31.657 score on a scale Standard Deviation 7.5764	30.815 score on a scale Standard Deviation 6.5633	30.319 score on a scale Standard Deviation 6.2328	—	—
Short-Form 36 Health Survey (SF-36) Score Bodily Pain Score: Wk 24 (n=118,108,87)	39.709 score on a scale Standard Deviation 9.2218	38.875 score on a scale Standard Deviation 8.3432	42.736 score on a scale Standard Deviation 9.7885	—	—
Short-Form 36 Health Survey (SF-36) Score Bodily Pain Score: Wk 48 (n=119,103,89)	41.318 score on a scale Standard Deviation 9.2879	40.836 score on a scale Standard Deviation 8.6176	43.105 score on a scale Standard Deviation 9.4713	—	—
Short-Form 36 Health Survey (SF-36) Score General Health Score: BL (n=127,116,90)	34.850 score on a scale Standard Deviation 9.5814	34.692 score on a scale Standard Deviation 9.3289	34.025 score on a scale Standard Deviation 8.8533	—	—
Short-Form 36 Health Survey (SF-36) Score General Health Score: Wk 24 (n=116,109,87)	39.644 score on a scale Standard Deviation 9.8338	39.805 score on a scale Standard Deviation 10.2346	39.050 score on a scale Standard Deviation 10.4236	—	—
Short-Form 36 Health Survey (SF-36) Score General Health Score: Wk 48 (n=118,101,89)	41.138 score on a scale Standard Deviation 10.3191	41.555 score on a scale Standard Deviation 9.9892	40.427 score on a scale Standard Deviation 10.5756	—	—
Short-Form 36 Health Survey (SF-36) Score Mental Health Score: BL (n=128,116,90)	38.443 score on a scale Standard Deviation 12.4207	38.307 score on a scale Standard Deviation 11.9908	38.405 score on a scale Standard Deviation 11.1899	—	—
Short-Form 36 Health Survey (SF-36) Score Mental Health Score: Wk 24 (n=118,108,87)	43.506 score on a scale Standard Deviation 11.5661	43.209 score on a scale Standard Deviation 10.7315	43.955 score on a scale Standard Deviation 10.6107	—	—
Short-Form 36 Health Survey (SF-36) Score Mental Health Score: Wk 48 (n=119,102,88)	44.529 score on a scale Standard Deviation 11.7796	44.447 score on a scale Standard Deviation 11.9128	43.640 score on a scale Standard Deviation 11.5868	—	—
Short-Form 36 Health Survey (SF-36) Score Physical Functioning Score: BL (n=127,116,91)	28.826 score on a scale Standard Deviation 9.5523	28.223 score on a scale Standard Deviation 9.8730	29.896 score on a scale Standard Deviation 8.7899	—	—
Short-Form 36 Health Survey (SF-36) Score Physical Functioning Score: Wk 24 (n=116,109,86)	34.286 score on a scale Standard Deviation 11.1702	33.929 score on a scale Standard Deviation 11.3543	37.323 score on a scale Standard Deviation 10.5428	—	—
Short-Form 36 Health Survey (SF-36) Score Physical Functioning Score: Wk 48 (n=118,103,89)	35.291 score on a scale Standard Deviation 11.7203	35.318 score on a scale Standard Deviation 10.6680	38.547 score on a scale Standard Deviation 11.6649	—	—
Short-Form 36 Health Survey (SF-36) Score Emotional Role Score: BL (n=127,115,90)	33.719 score on a scale Standard Deviation 13.9238	32.217 score on a scale Standard Deviation 11.9819	32.167 score on a scale Standard Deviation 13.6914	—	—
Short-Form 36 Health Survey (SF-36) Score Emotional Role Score: Wk 24 (n=117,109,87)	39.665 score on a scale Standard Deviation 13.1752	37.406 score on a scale Standard Deviation 13.2790	39.928 score on a scale Standard Deviation 13.4008	—	—
Short-Form 36 Health Survey (SF-36) Score Emotional Role Score: Wk 48 (n=118,102,88)	40.429 score on a scale Standard Deviation 13.7266	39.644 score on a scale Standard Deviation 12.7514	39.800 score on a scale Standard Deviation 14.0611	—	—
Short-Form 36 Health Survey (SF-36) Score Physical Role Score: BL (n=127,116,90)	31.013 score on a scale Standard Deviation 9.5785	30.864 score on a scale Standard Deviation 8.7546	32.309 score on a scale Standard Deviation 9.4529	—	—
Short-Form 36 Health Survey (SF-36) Score Social Functioning Score: BL (n=128,116,91)	34.948 score on a scale Standard Deviation 11.6147	33.341 score on a scale Standard Deviation 11.3817	35.812 score on a scale Standard Deviation 12.2109	—	—
Short-Form 36 Health Survey (SF-36) Score Social Functioning Score: Wk 24 (n=118,109,87)	40.765 score on a scale Standard Deviation 10.5247	40.737 score on a scale Standard Deviation 10.4537	42.869 score on a scale Standard Deviation 10.8028	—	—
Short-Form 36 Health Survey (SF-36) Score Social Functioning Score: Wk 48 (n=119,103,89)	42.366 score on a scale Standard Deviation 11.1916	42.235 score on a scale Standard Deviation 11.0464	43.613 score on a scale Standard Deviation 11.3599	—	—
Short-Form 36 Health Survey (SF-36) Score Vitality Score: BL (n=128,116,91)	38.253 score on a scale Standard Deviation 10.2709	38.096 score on a scale Standard Deviation 9.5184	39.832 score on a scale Standard Deviation 10.2209	—	—
Short-Form 36 Health Survey (SF-36) Score Vitality Score: Wk 24 (n=118,109,87)	45.000 score on a scale Standard Deviation 10.7039	44.577 score on a scale Standard Deviation 11.1008	46.206 score on a scale Standard Deviation 10.0519	—	—
Short-Form 36 Health Survey (SF-36) Score Vitality Score: Wk 48 (n=119,103,87)	46.905 score on a scale Standard Deviation 10.5538	46.251 score on a scale Standard Deviation 10.8299	47.462 score on a scale Standard Deviation 11.3098	—	—

SECONDARY outcome

Timeframe: BL, Weeks 24 and 48

Population: ITT-M2 population, n = number of participants analyzed for the given parameter at the specified timepoint.

SF-36 scores were obtained by scoring participants' responses to a 36 item questionnaire. SF-36 evaluated 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health from a range of 1 (better) to 5 (worst). The score for each section was an average of the individual question scores, which were scaled 0-100 (100=highest level of functioning). These 8 aspects were summarized as physical and mental component scores.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=116 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=108 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=88 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Change in SF-36 Score From BL Physical Functioning Score: Wk 24 (n=111,108,85)	5.517 score on a scale Standard Deviation 7.6418	6.261 score on a scale Standard Deviation 8.2243	7.081 score on a scale Standard Deviation 9.4105	—	—
Change in SF-36 Score From BL Physical Functioning Score: Wk 48 (n=114,102,88)	6.529 score on a scale Standard Deviation 8.6382	6.318 score on a scale Standard Deviation 9.8785	8.577 score on a scale Standard Deviation 10.9439	—	—
Change in SF-36 Score From BL Emotional Role Score: Wk 24 (n=113,108,85)	5.951 score on a scale Standard Deviation 11.9256	4.571 score on a scale Standard Deviation 12.5182	7.180 score on a scale Standard Deviation 12.0934	—	—
Change in SF-36 Score From BL Emotional Role Score: Wk 48 (n=114,101,86)	6.445 score on a scale Standard Deviation 14.0187	6.350 score on a scale Standard Deviation 12.4357	7.142 score on a scale Standard Deviation 13.4771	—	—
Change in SF-36 Score From BL Physical Role Score: Wk 24 (n=113,108,84)	6.473 score on a scale Standard Deviation 9.1079	5.994 score on a scale Standard Deviation 9.7472	6.385 score on a scale Standard Deviation 9.6101	—	—
Change in SF-36 Score From BL Physical Role Score: Wk 48 (n=115,101,87)	7.347 score on a scale Standard Deviation 10.0663	7.493 score on a scale Standard Deviation 9.8317	7.873 score on a scale Standard Deviation 9.6133	—	—
Change in SF-36 Score From BL Social Functioning Score: Wk 24 (n=115,108,86	5.786 score on a scale Standard Deviation 9.8861	7.070 score on a scale Standard Deviation 11.1663	6.722 score on a scale Standard Deviation 9.8518	—	—
Change in SF-36 Score From BL Social Functioning Score: Wk 48 (n=116,102,88)	7.382 score on a scale Standard Deviation 10.9376	7.807 score on a scale Standard Deviation 11.1880	7.713 score on a scale Standard Deviation 11.3046	—	—
Change in SF-36 Score From BL Vitality Score: Wk 24 (n=115,108,86)	6.796 score on a scale Standard Deviation 10.7057	6.495 score on a scale Standard Deviation 10.2488	6.534 score on a scale Standard Deviation 8.8644	—	—
Change in SF-36 Score From BL Vitality Score: Wk 48 (n=116,102,86)	9.088 score on a scale Standard Deviation 10.6821	7.479 score on a scale Standard Deviation 10.2350	7.200 score on a scale Standard Deviation 10.3652	—	—
Change in SF-36 Score From BL Bodily Pain Score: Wk 24 (n=115,106,85)	8.180 score on a scale Standard Deviation 9.7621	7.914 score on a scale Standard Deviation 8.7302	11.948 score on a scale Standard Deviation 10.2846	—	—
Change in SF-36 Score From BL Bodily Pain Score: Wk 48 (n=116,101,87)	9.815 score on a scale Standard Deviation 9.4616	9.323 score on a scale Standard Deviation 9.3335	12.712 score on a scale Standard Deviation 10.3962	—	—
Change in SF-36 Score From BL General Health Score: Wk 24 (n=112,108,85)	4.941 score on a scale Standard Deviation 8.8122	4.996 score on a scale Standard Deviation 8.7345	4.812 score on a scale Standard Deviation 8.1955	—	—
Change in SF-36 Score From BL General Health Score: Wk 48 (n=115,100,87)	6.470 score on a scale Standard Deviation 8.9736	6.340 score on a scale Standard Deviation 8.9124	6.241 score on a scale Standard Deviation 8.4496	—	—
Change in SF-36 Score From BL Mental Health Score: Wk 24 (n=115,107,85)	5.173 score on a scale Standard Deviation 10.5160	4.138 score on a scale Standard Deviation 11.5165	5.312 score on a scale Standard Deviation 8.1965	—	—
Change in SF-36 Score From BL Mental Health Score: Wk 48 (n=116,101,86)	6.607 score on a scale Standard Deviation 10.6356	4.979 score on a scale Standard Deviation 12.3225	4.939 score on a scale Standard Deviation 11.0695	—	—

SECONDARY outcome

Timeframe: Days 1 and 15 (before infusion and 30 minutes following infusion) and Weeks 4, 8, 16, 24, 26, 28, 32, 40, and 48 or early withdrawal and at Weeks 24 and 48 of safety follow-up (1 year period following the completion of study treatment).

Population: ITT-M2 population, n = number of participants analyzed for the given parameter at the specified timepoint.

Cfirst values were estimated from rituximab serum concentrations by non-compartmental methods using the software WinNonlin Enterprise Version 5.2.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=121 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=112 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=91 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Maximum Observed Serum Concentrations Following the 1st Infusion of Rituximab (Cfirst) in the 1st and 2nd Courses of Treatment in Micrograms Per mL (µg/mL) First Course (n=121,112,91)	165 µg/mL Standard Deviation 42	163 µg/mL Standard Deviation 39	317 µg/mL Standard Deviation 94	—	—
Maximum Observed Serum Concentrations Following the 1st Infusion of Rituximab (Cfirst) in the 1st and 2nd Courses of Treatment in Micrograms Per mL (µg/mL) Second Course (n=120,105,84)	177 µg/mL Standard Deviation 41	345 µg/mL Standard Deviation 92	350 µg/mL Standard Deviation 86	—	—

SECONDARY outcome

Timeframe: Days 1 and 15 (before infusion and 30 minutes following infusion) and Weeks 4, 8, 16, 24, 26, 28, 32, 40, and 48 or early withdrawal and at Weeks 24 and 48 of safety follow-up (1 year period following the completion of study treatment).

Population: ITT-M2 population, n = number of participants assessed for the given parameter at the specified timepoint.

Csecond values were estimated from rituximab serum concentrations by non-compartmental methods using the software WinNonlin Enterprise Version 5.2.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=130 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=116 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=90 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Maximum Observed Serum Concentrations Following the 2nd Infusion of Rituximab (Csecond) in the 1st and 2nd Courses of Treatment in µg/mL First course (n=130,116,90)	194 µg/mL Standard Deviation 65	190 µg/mL Standard Deviation 57	373 µg/mL Standard Deviation 116	—	—
Maximum Observed Serum Concentrations Following the 2nd Infusion of Rituximab (Csecond) in the 1st and 2nd Courses of Treatment in µg/mL Second course (n=121,107,88)	209 µg/mL Standard Deviation 70	380 µg/mL Standard Deviation 139	392 µg/mL Standard Deviation 123	—	—

SECONDARY outcome

Timeframe: Days 1 and 15 (before infusion and 30 minutes following infusion) and Weeks 4, 8, 16, 24, 26, 28, 32, 40, and 48 or early withdrawal and at Weeks 24 and 48 of safety follow-up (1 year period following the completion of study treatment).

Population: ITT-M2 population, n = number of participants assessed for the given parameter at the specified timepoint.

t1/2 values were estimated from rituximab serum concentrations by non-compartmental methods using the software WinNonlin Enterprise Version 5.2.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=120 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=109 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=85 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Terminal Elimination Half-Life (t1/2) in the 1st and 2nd Courses of Treatment in Days First Course (n=120,109,85)	16.04 days Standard Deviation 5.52	16.75 days Standard Deviation 6.64	17.67 days Standard Deviation 6.00	—	—
Terminal Elimination Half-Life (t1/2) in the 1st and 2nd Courses of Treatment in Days Second Course (n=116,99,85)	19.62 days Standard Deviation 6.05	22.13 days Standard Deviation 6.48	21.42 days Standard Deviation 6.32	—	—

SECONDARY outcome

Timeframe: BL

Population: ITT-M2 population. 7, 8, 3, 1, and 2 participants were not analyzed for this outcome measure from the Low Dose, Escalated Dose, High Dose, Placebo, and Decreased Dose groups, respectively.

Surface expression of CD19 was assessed by fluorescence-activated cell sorting (FACS) analysis as a marker of absolute B lymphocyte count.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=127 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=111 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=90 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate n=5 Participants Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate n=23 Participants Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Peripheral Cluster of Differentiation (CD) 19 Positive (+) B Cell Count at BL in Cells Per Microliter (Cells/µL)	183.6 cells/µL Standard Deviation 142.31	168.9 cells/µL Standard Deviation 94.98	205.3 cells/µL Standard Deviation 171.91	318.2 cells/µL Standard Deviation 174.62	235.4 cells/µL Standard Deviation 112.56

SECONDARY outcome

Timeframe: BL, Days 1 and 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48

Population: ITT-M2 population, n = number of participants assessed for the given parameter at the specified timepoint.

Surface expression of CD19 was assessed by FACS analysis as a marker of absolute B lymphocyte count. The LLN was defined as < 80 cells/µL.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=127 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=114 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=91 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate n=6 Participants Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate n=24 Participants Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) Day 15 Predose (n=127,114,87,5,24)	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) Day 15 Postdose (n=121,108,89,6,23)	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) Wk 4 (n=127,111,87,6,24)	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) Wk 8 (n=126,111,90,6,23)	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) Wk 16 (n=122,112,91,6,23)	0.8 percentage of participants	0.9 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) Wk 24 (n=114,107,87,4,24)	7.0 percentage of participants	6.5 percentage of participants	4.6 percentage of participants	0.0 percentage of participants	12.5 percentage of participants
Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) Wk 28 (n=121,103,86,6,25)	0.8 percentage of participants	0.0 percentage of participants	2.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) Wk 32 (n=122,107,88,5,24)	2.5 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	20.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) Wk 40 (n=118,103,84,4,23)	0.8 percentage of participants	1.0 percentage of participants	0.0 percentage of participants	50.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) Wk 48 (n=118,105,89,4,22)	5.9 percentage of participants	1.9 percentage of participants	5.6 percentage of participants	50.0 percentage of participants	13.6 percentage of participants
Percentage of Participants With Peripheral CD19+ B Cell Counts Above BL or the Lower Limit of Normal (LLN) Day 1 Postdose (n=118,109,85,5,23)	0.8 percentage of participants	0.0 percentage of participants	2.4 percentage of participants	0.0 percentage of participants	8.7 percentage of participants

SECONDARY outcome

Timeframe: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48

Population: The safety analysis population (SAP) = ITT-M2 population, n = number of participants assessed for the given parameter at the specified timepoint.

Surface expression of CD20 was assessed by FACS analysis as a marker of mature and memory B lymphocyte count.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=113 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=101 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=75 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Peripheral CD20+ B Cell Count in Cells/µL BL Predose (n=113,97,75)	184.8 cells/µL Standard Deviation 135.29	173.4 cells/µL Standard Deviation 99.18	218.1 cells/µL Standard Deviation 158.16	—	—
Peripheral CD20+ B Cell Count in Cells/µL BL Postdose (n=105,94,71)	0.2 cells/µL Standard Deviation 0.58	0.2 cells/µL Standard Deviation 0.49	0.2 cells/µL Standard Deviation 0.65	—	—
Peripheral CD20+ B Cell Count in Cells/µL Day 15 Predose (n=112,101,75)	0.6 cells/µL Standard Deviation 1.76	0.4 cells/µL Standard Deviation 0.74	0.3 cells/µL Standard Deviation 0.57	—	—
Peripheral CD20+ B Cell Count in Cells/µL Day 15 Postdose (n=104,91,70)	1.0 cells/µL Standard Deviation 7.35	0.2 cells/µL Standard Deviation 0.63	0.1 cells/µL Standard Deviation 0.39	—	—
Peripheral CD20+ B Cell Count in Cells/µL Wk 4 (n=110,95,72)	0.6 cells/µL Standard Deviation 3.21	0.2 cells/µL Standard Deviation 0.50	0.3 cells/µL Standard Deviation 0.74	—	—
Peripheral CD20+ B Cell Count in Cells/µL Wk 8 (n=111,92,73)	0.3 cells/µL Standard Deviation 0.64	4.9 cells/µL Standard Deviation 42.09	0.3 cells/µL Standard Deviation 0.86	—	—
Peripheral CD20+ B Cell Count in Cells/µL Wk 16 (n=105,93,75)	2.4 cells/µL Standard Deviation 8.02	3.0 cells/µL Standard Deviation 8.67	0.9 cells/µL Standard Deviation 3.15	—	—
Peripheral CD20+ B Cell Count in Cells/µL Wk 24 (n=99,92,67)	20.2 cells/µL Standard Deviation 53.56	15.2 cells/µL Standard Deviation 25.98	13.2 cells/µL Standard Deviation 23.96	—	—
Peripheral CD20+ B Cell Count in Cells/µL Wk 28 (n=101,85,72)	1.5 cells/µL Standard Deviation 12.14	1.1 cells/µL Standard Deviation 5.82	4.5 cells/µL Standard Deviation 20.59	—	—
Peripheral CD20+ B Cell Count in Cells/µL Wk 32 (n=107,88,74)	5.1 cells/µL Standard Deviation 33.42	1.1 cells/µL Standard Deviation 4.93	1.1 cells/µL Standard Deviation 6.88	—	—
Peripheral CD20+ B Cell Count in Cells/µL Wk 40 (n=100,86,68)	1.4 cells/µL Standard Deviation 5.44	1.7 cells/µL Standard Deviation 7.94	1.6 cells/µL Standard Deviation 9.11	—	—
Peripheral CD20+ B Cell Count in Cells/µL Wk 48 (n=100,89,73)	12.4 cells/µL Standard Deviation 26.89	4.4 cells/µL Standard Deviation 10.70	8.2 cells/µL Standard Deviation 22.12	—	—

SECONDARY outcome

Timeframe: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48

Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.

Surface expression of CD22 was assessed by FACS analysis as a marker of mature lymphocyte count.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=113 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=101 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=75 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Peripheral CD22+ B Cell Count in Cells/µL Day 15 Postdose (n=104,91,70)	1.9 cells/µL Standard Deviation 1.92	1.9 cells/µL Standard Deviation 1.77	2.4 cells/µL Standard Deviation 3.23	—	—
Peripheral CD22+ B Cell Count in Cells/µL BL Predose (n=113,97,75)	188.0 cells/µL Standard Deviation 135.54	177.1 cells/µL Standard Deviation 98.69	221.6 cells/µL Standard Deviation 158.82	—	—
Peripheral CD22+ B Cell Count in Cells/µL BL Postdose (n=105,94,71)	24.5 cells/µL Standard Deviation 20.59	23.2 cells/µL Standard Deviation 17.39	29.0 cells/µL Standard Deviation 31.51	—	—
Peripheral CD22+ B Cell Count in Cells/µL Day 15 Predose (n=112,101,75)	5.0 cells/µL Standard Deviation 6.33	5.0 cells/µL Standard Deviation 6.03	5.1 cells/µL Standard Deviation 6.30	—	—
Peripheral CD22+ B Cell Count in Cells/µL Wk 4 (n=110,95,72)	4.1 cells/µL Standard Deviation 5.61	3.8 cells/µL Standard Deviation 5.44	4.0 cells/µL Standard Deviation 7.73	—	—
Peripheral CD22+ B Cell Count in Cells/µL Wk 8 (n=111,92,73)	3.6 cells/µL Standard Deviation 5.14	8.4 cells/µL Standard Deviation 41.87	3.9 cells/µL Standard Deviation 6.03	—	—
Peripheral CD22+ B Cell Count in Cells/µL Wk 16 (n=105,93,75)	5.1 cells/µL Standard Deviation 8.60	6.1 cells/µL Standard Deviation 9.83	3.6 cells/µL Standard Deviation 5.94	—	—
Peripheral CD22+ B Cell Count in Cells/µL Wk 24 (n=99,92,67)	20.1 cells/µL Standard Deviation 32.29	17.6 cells/µL Standard Deviation 25.81	16.6 cells/µL Standard Deviation 25.70	—	—
Peripheral CD22+ B Cell Count in Cells/µL Wk 28 (n=101,85,72)	4.2 cells/µL Standard Deviation 13.16	4.0 cells/µL Standard Deviation 8.07	8.2 cells/µL Standard Deviation 21.96	—	—
Peripheral CD22+ B Cell Count in Cells/µL Wk 32 (n=107,88,74)	8.0 cells/µL Standard Deviation 33.71	3.7 cells/µL Standard Deviation 8.58	3.6 cells/µL Standard Deviation 8.51	—	—
Peripheral CD22+ B Cell Count in Cells/µL Wk 40 (n=100,86,68)	3.7 cells/µL Standard Deviation 6.92	3.5 cells/µL Standard Deviation 8.05	4.0 cells/µL Standard Deviation 10.01	—	—
Peripheral CD22+ B Cell Count in Cells/µL Wk 48 (n=100,89,73)	14.3 cells/µL Standard Deviation 26.88	6.3 cells/µL Standard Deviation 10.77	9.8 cells/µL Standard Deviation 22.24	—	—

SECONDARY outcome

Timeframe: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48

Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.

Simultaneous surface expression of CD19 and CD27 was assessed by FACS analysis as a marker of memory B lymphocyte count.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=113 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=99 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=75 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Peripheral CD19+CD27+ B Cell Count in Cells/µL Wk 8 (n=110,92,75)	4.6 cells/µL Standard Deviation 2.98	4.3 cells/µL Standard Deviation 2.51	4.6 cells/µL Standard Deviation 2.73	—	—
Peripheral CD19+CD27+ B Cell Count in Cells/µL BL Predose (n=113,98,75)	41.4 cells/µL Standard Deviation 41.79	42.2 cells/µL Standard Deviation 40.74	42.3 cells/µL Standard Deviation 33.71	—	—
Peripheral CD19+CD27+ B Cell Count in Cells/µL BL Postdose (n=105,94,72)	4.6 cells/µL Standard Deviation 2.85	5.1 cells/µL Standard Deviation 4.20	4.7 cells/µL Standard Deviation 3.40	—	—
Peripheral CD19+CD27+ B Cell Count in Cells/µL Day 15 Predose (n=112,99,75)	5.1 cells/µL Standard Deviation 4.65	4.5 cells/µL Standard Deviation 3.40	4.5 cells/µL Standard Deviation 2.83	—	—
Peripheral CD19+CD27+ B Cell Count in Cells/µL Day 15 Postdose (n=103,89,70)	3.0 cells/µL Standard Deviation 0.20	3.0 cells/µL Standard Deviation 0.24	3.0 cells/µL Standard Deviation 0.27	—	—
Peripheral CD19+CD27+ B Cell Count in Cells/µL Wk 4 (n=110,92,74)	4.6 cells/µL Standard Deviation 3.56	4.0 cells/µL Standard Deviation 2.70	4.6 cells/µL Standard Deviation 4.57	—	—
Peripheral CD19+CD27+ B Cell Count in Cells/µL Wk 16 (n=104,93,75)	5.5 cells/µL Standard Deviation 4.20	5.5 cells/µL Standard Deviation 4.39	4.9 cells/µL Standard Deviation 4.33	—	—
Peripheral CD19+CD27+ B Cell Count in Cells/µL Wk 24 (n=97,91,67)	6.8 cells/µL Standard Deviation 4.67	6.8 cells/µL Standard Deviation 5.95	7.1 cells/µL Standard Deviation 5.80	—	—
Peripheral CD19+CD27+ B Cell Count in Cells/µL Wk 28 (n=101,86,72)	5.3 cells/µL Standard Deviation 3.97	4.8 cells/µL Standard Deviation 3.54	4.1 cells/µL Standard Deviation 2.51	—	—
Peripheral CD19+CD27+ B Cell Count in Cells/µL Wk 32 (n=105,88,73)	5.7 cells/µL Standard Deviation 5.35	4.5 cells/µL Standard Deviation 3.38	5.3 cells/µL Standard Deviation 4.14	—	—
Peripheral CD19+CD27+ B Cell Count in Cells/µL Wk 40 (n=99,84,67)	5.6 cells/µL Standard Deviation 6.24	4.7 cells/µL Standard Deviation 3.41	4.9 cells/µL Standard Deviation 4.28	—	—
Peripheral CD19+CD27+ B Cell Count in Cells/µL Wk 48 (n=96,87,70)	5.4 cells/µL Standard Deviation 4.04	5.3 cells/µL Standard Deviation 4.11	6.5 cells/µL Standard Deviation 11.94	—	—

SECONDARY outcome

Timeframe: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48

Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.

Surface expression of CD19 in the absence of CD27 expression was assessed by FACS analysis as a marker of naive B lymphocyte count.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=113 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=99 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=75 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL Wk 8 (n=110,92,75)	10.1 cells/µL Standard Deviation 0.49	10.1 cells/µL Standard Deviation 0.44	10.4 cells/µL Standard Deviation 1.77	—	—
Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL Wk 16 (n=104,93,75)	11.3 cells/µL Standard Deviation 6.65	11.7 cells/µL Standard Deviation 6.55	10.5 cells/µL Standard Deviation 2.04	—	—
Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL Wk 24 (n=97,91,67)	23.3 cells/µL Standard Deviation 25.11	21.7 cells/µL Standard Deviation 23.50	20.8 cells/µL Standard Deviation 20.89	—	—
Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL Wk 28 (n=101,86,72)	11.0 cells/µL Standard Deviation 9.15	10.5 cells/µL Standard Deviation 3.30	13.7 cells/µL Standard Deviation 19.34	—	—
Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL Wk 32 (n=105,88,73)	13.8 cells/µL Standard Deviation 27.58	10.9 cells/µL Standard Deviation 4.07	10.7 cells/µL Standard Deviation 5.86	—	—
Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL Wk 40 (n=99,84,67)	10.7 cells/µL Standard Deviation 4.33	11.3 cells/µL Standard Deviation 8.70	11.0 cells/µL Standard Deviation 7.59	—	—
Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL Wk 48 (n=96,87,70)	18.8 cells/µL Standard Deviation 22.13	13.0 cells/µL Standard Deviation 11.67	15.8 cells/µL Standard Deviation 18.69	—	—
Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL BL Predose (n=113,98,75)	141.1 cells/µL Standard Deviation 108.90	126.4 cells/µL Standard Deviation 75.00	179.3 cells/µL Standard Deviation 169.38	—	—
Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL BL Postdose (n=105,94,72)	16.7 cells/µL Standard Deviation 13.10	15.2 cells/µL Standard Deviation 9.5	19.3 cells/µL Standard Deviation 21.92	—	—
Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL Day 15 Predose (n=112,99,75)	10.2 cells/µL Standard Deviation 1.39	10.2 cells/µL Standard Deviation 0.94	10.2 cells/µL Standard Deviation 1.07	—	—
Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL Day 15 Postdose (n=103,89,70)	10.0 cells/µL Standard Deviation 0.00	10.0 cells/µL Standard Deviation 0.00	10.0 cells/µL Standard Deviation 0.00	—	—
Peripheral CD19+CD27 Negative (-) B Cell Count in Cells/µL Wk 4 (n=110,92,74)	10.1 cells/µL Standard Deviation 0.90	10.1 cells/µL Standard Deviation 0.56	10.4 cells/µL Standard Deviation 1.68	—	—

SECONDARY outcome

Timeframe: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48

Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.

Surface expression of CD3 was assessed by FACS analysis as a marker of absolute T lymphocyte count. The normal range of CD3+ T cells was defined as 723-2737 cells/µL.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=127 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=114 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=91 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Peripheral CD3+ T Cell Count in Cells/µL BL Predose (n=127,110,90)	1262.1 cells/µL Standard Deviation 651.88	1229.6 cells/µL Standard Deviation 565.79	1319.7 cells/µL Standard Deviation 569.57	—	—
Peripheral CD3+ T Cell Count in Cells/µL BL Postdose (n=118,109,85)	237.8 cells/µL Standard Deviation 133.09	263.4 cells/µL Standard Deviation 167.58	226.9 cells/µL Standard Deviation 122.02	—	—
Peripheral CD3+ T Cell Count in Cells/µL Day 15 Predose (n=127,114,87)	1282.4 cells/µL Standard Deviation 587.75	1292.5 cells/µL Standard Deviation 589.57	1356.0 cells/µL Standard Deviation 604.98	—	—
Peripheral CD3+ T Cell Count in Cells/µL Day 15 Postdose (n=121,108,89)	302.5 cells/µL Standard Deviation 149.80	350.0 cells/µL Standard Deviation 220.23	343.3 cells/µL Standard Deviation 184.44	—	—
Peripheral CD3+ T Cell Count in Cells/µL Wk 4 (n=127,111,87)	1231.0 cells/µL Standard Deviation 585.60	1193.6 cells/µL Standard Deviation 505.68	1264.8 cells/µL Standard Deviation 508.87	—	—
Peripheral CD3+ T Cell Count in Cells/µL Wk 8 (n=126,111,90)	1262.8 cells/µL Standard Deviation 643.60	1317.3 cells/µL Standard Deviation 629.87	1296.0 cells/µL Standard Deviation 534.19	—	—
Peripheral CD3+ T Cell Count in Cells/µL Wk 16 (n=122,112,91)	1256.0 cells/µL Standard Deviation 580.95	1317.1 cells/µL Standard Deviation 605.57	1260.2 cells/µL Standard Deviation 562.16	—	—
Peripheral CD3+ T Cell Count in Cells/µL Wk 24 (n=113,107,85)	1332.1 cells/µL Standard Deviation 658.82	1297.1 cells/µL Standard Deviation 602.07	1314.9 cells/µL Standard Deviation 511.18	—	—
Peripheral CD3+ T Cell Count in Cells/µL Wk 28 (n=120,101,86)	1300.3 cells/µL Standard Deviation 670.68	1223.6 cells/µL Standard Deviation 505.72	1327.7 cells/µL Standard Deviation 590.38	—	—
Peripheral CD3+ T Cell Count in Cells/µL Wk 32 (n=122,107,88)	1318.8 cells/µL Standard Deviation 650.01	1286.0 cells/µL Standard Deviation 522.82	1312.6 cells/µL Standard Deviation 509.52	—	—
Peripheral CD3+ T Cell Count in Cells/µL Wk 40 (n=118,103,84)	1283.9 cells/µL Standard Deviation 620.88	1293.9 cells/µL Standard Deviation 559.38	1306.4 cells/µL Standard Deviation 508.49	—	—
Peripheral CD3+ T Cell Count in Cells/µL Wk 48 (n=114,103,83)	1280.6 cells/µL Standard Deviation 622.21	1251.8 cells/µL Standard Deviation 511.15	1315.8 cells/µL Standard Deviation 598.66	—	—

SECONDARY outcome

Timeframe: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48

Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.

Surface expression of CD3 was assessed by FACS analysis as a marker of absolute T lymphocyte count. The normal range of CD3+ T cells was defined as 723-2737 cells/µL.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=122 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=107 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=88 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Change From BL in Peripheral CD3+ T Cell Count Wk 48 (n=110,96,80)	-9.4 cells/µL Standard Deviation 538.12	20.3 cells/µL Standard Deviation 431.58	-12.4 cells/µL Standard Deviation 502.20	—	—
Change From BL in Peripheral CD3+ T Cell Count BL Postdose (n=115,106,82)	-1000.6 cells/µL Standard Deviation 576.77	-968.8 cells/µL Standard Deviation 539.80	-1065.4 cells/µL Standard Deviation 513.18	—	—
Change From BL in Peripheral CD3+ T Cell Count Day 15 Predose (n=122,107,84)	25.2 cells/µL Standard Deviation 478.94	40.8 cells/µL Standard Deviation 435.72	34.0 cells/µL Standard Deviation 463.99	—	—
Change From BL in Peripheral CD3+ T Cell Count Day 15 Postdose (n=116,102,86)	-952.6 cells/µL Standard Deviation 572.95	-897.3 cells/µL Standard Deviation 535.33	-965.9 cells/µL Standard Deviation 500.78	—	—
Change From BL in Peripheral CD3+ T Cell Count Wk 4 (n=122,105,84)	-31.9 cells/µL Standard Deviation 427.92	-19.6 cells/µL Standard Deviation 450.67	-53.3 cells/µL Standard Deviation 476.03	—	—
Change From BL in Peripheral CD3+ T Cell Count Wk 8 (n=121,105,87)	3.4 cells/µL Standard Deviation 548.80	98.8 cells/µL Standard Deviation 496.83	-23.6 cells/µL Standard Deviation 429.32	—	—
Change From BL in Peripheral CD3+ T Cell Count Wk 16 (n=117,105,88)	-24.5 cells/µL Standard Deviation 517.71	81.8 cells/µL Standard Deviation 436.08	-47.4 cells/µL Standard Deviation 506.89	—	—
Change From BL in Peripheral CD3+ T Cell Count Wk 24 (n=109,100,82)	78.1 cells/µL Standard Deviation 511.99	47.7 cells/µL Standard Deviation 448.72	-0.8 cells/µL Standard Deviation 444.81	—	—
Change From BL in Peripheral CD3+ T Cell Count Wk 28 (n=115,94,84)	41.4 cells/µL Standard Deviation 599.47	20.1 cells/µL Standard Deviation 379.99	-0.4 cells/µL Standard Deviation 488.79	—	—
Change From BL in Peripheral CD3+ T Cell Count Wk 32 (n=116,99,85)	47.9 cells/µL Standard Deviation 557.67	51.2 cells/µL Standard Deviation 412.36	-18.4 cells/µL Standard Deviation 439.47	—	—
Change From BL in Peripheral CD3+ T Cell Count Wk 40 (n=113,96,81)	33.5 cells/µL Standard Deviation 517.70	65.1 cells/µL Standard Deviation 511.46	-12.7 cells/µL Standard Deviation 421.39	—	—

SECONDARY outcome

Timeframe: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48

Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.

Surface expression of CD4 was assessed by FACS analysis as a marker of T helper cell count. The normal range of CD4+ T cells was defined as 404-1612 cells/µL.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=127 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=114 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=91 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Peripheral CD4+ T Cell Count in Cells/µL BL Predose (n=127,110,90)	900.4 cells/µL Standard Deviation 500.42	876.7 cells/µL Standard Deviation 398.85	953.6 cells/µL Standard Deviation 462.18	—	—
Peripheral CD4+ T Cell Count in Cells/µL BL Postdose (n=118,109,85)	130.2 cells/µL Standard Deviation 81.65	145.9 cells/µL Standard Deviation 86.22	129.8 cells/µL Standard Deviation 75.17	—	—
Peripheral CD4+ T Cell Count in Cells/µL Day 15 Predose (n=127,114,87)	920.2 cells/µL Standard Deviation 468.01	930.1 cells/µL Standard Deviation 424.72	991.9 cells/µL Standard Deviation 504.25	—	—
Peripheral CD4+ T Cell Count in Cells/µL Day 15 Postdose (n=121,108,89)	165.4 cells/µL Standard Deviation 92.96	196.7 cells/µL Standard Deviation 124.38	196.9 cells/µL Standard Deviation 132.65	—	—
Peripheral CD4+ T Cell Count in Cells/µL Wk 4 (n=127,111,87)	880.5 cells/µL Standard Deviation 456.63	859.7 cells/µL Standard Deviation 373.69	917.9 cells/µL Standard Deviation 431.93	—	—
Peripheral CD4+ T Cell Count in Cells/µL Wk 8 (n=126,111,90)	903.3 cells/µL Standard Deviation 514.94	949.2 cells/µL Standard Deviation 462.71	950.5 cells/µL Standard Deviation 458.27	—	—
Peripheral CD4+ T Cell Count in Cells/µL Wk 16 (n=122,112,91)	889.2 cells/µL Standard Deviation 436.84	937.8 cells/µL Standard Deviation 450.52	910.1 cells/µL Standard Deviation 472.95	—	—
Peripheral CD4+ T Cell Count in Cells/µL Wk 24 (n=113,107,85)	969.6 cells/µL Standard Deviation 553.17	918.4 cells/µL Standard Deviation 434.08	948.2 cells/µL Standard Deviation 418.09	—	—
Peripheral CD4+ T Cell Count in Cells/µL Wk 28 (n=120,101,86)	936.6 cells/µL Standard Deviation 539.94	870.2 cells/µL Standard Deviation 373.17	967.0 cells/µL Standard Deviation 496.62	—	—
Peripheral CD4+ T Cell Count in Cells/µL Wk 32 (n=122,107,88)	939.0 cells/µL Standard Deviation 515.71	911.6 cells/µL Standard Deviation 404.40	950.9 cells/µL Standard Deviation 439.04	—	—
Peripheral CD4+ T Cell Count in Cells/µL Wk 40 (n=118,103,84)	908.7 cells/µL Standard Deviation 478.40	901.9 cells/µL Standard Deviation 383.73	942.6 cells/µL Standard Deviation 422.23	—	—
Peripheral CD4+ T Cell Count in Cells/µL Wk 48 (n=114,103,83)	908.2 cells/µL Standard Deviation 477.46	889.8 cells/µL Standard Deviation 378.08	952.7 cells/µL Standard Deviation 487.98	—	—

SECONDARY outcome

Timeframe: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48

Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.

Surface expression of CD4 was assessed by FACS analysis as a marker of T helper cell count. The normal range of CD4+ T cells was defined as 404-1612 cells/µL.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=122 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=107 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=88 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Change From BL in Peripheral CD4+ T Cell Count BL Postdose (n=115,106,82)	-744.6 cells/µL Standard Deviation 454.55	-738.1 cells/µL Standard Deviation 393.02	-801.2 cells/µL Standard Deviation 416.45	—	—
Change From BL in Peripheral CD4+ T Cell Count Day 15 Predose (n=122,107,84)	24.3 cells/µL Standard Deviation 355.22	38.9 cells/µL Standard Deviation 306.89	36.0 cells/µL Standard Deviation 359.92	—	—
Change From BL in Peripheral CD4+ T Cell Count Day 15 Postdose (n=116,102,86)	-732.2 cells/µL Standard Deviation 449.99	-696.5 cells/µL Standard Deviation 392.37	-749.4 cells/µL Standard Deviation 401.01	—	—
Change From BL in Peripheral CD4+ T Cell Count Wk 4 (n=122,105,84)	-16.1 cells/µL Standard Deviation 330.20	-4.2 cells/µL Standard Deviation 345.57	-36.2 cells/µL Standard Deviation 368.83	—	—
Change From BL in Peripheral CD4+ T Cell Count Wk 8 (n=121,105,87)	7.9 cells/µL Standard Deviation 418.85	84.1 cells/µL Standard Deviation 370.64	-4.4 cells/µL Standard Deviation 343.31	—	—
Change From BL in Peripheral CD4+ T Cell Count Wk 16 (n=117,105,88)	-24.3 cells/µL Standard Deviation 377.76	64.0 cells/µL Standard Deviation 349.16	-33.4 cells/µL Standard Deviation 407.52	—	—
Change From BL in Peripheral CD4+ T Cell Count Wk 24 (n=109,100,82)	72.6 cells/µL Standard Deviation 395.29	37.3 cells/µL Standard Deviation 312.15	-0.7 cells/µL Standard Deviation 336.19	—	—
Change From BL in Peripheral CD4+ T Cell Count Wk 28 (n=115,94,84)	42.8 cells/µL Standard Deviation 446.65	13.5 cells/µL Standard Deviation 276.55	7.4 cells/µL Standard Deviation 377.73	—	—
Change From BL in Peripheral CD4+ T Cell Count Wk 32 (n=116,99,85)	38.4 cells/µL Standard Deviation 419.78	39.2 cells/µL Standard Deviation 305.18	-8.4 cells/µL Standard Deviation 337.42	—	—
Change From BL in Peripheral CD4+ T Cell Count Wk 40 (n=113,96,81)	14.9 cells/µL Standard Deviation 375.97	39.5 cells/µL Standard Deviation 356.89	-6.4 cells/µL Standard Deviation 331.87	—	—
Change From BL in Peripheral CD4+ T Cell Count Wk 48 (n=110,96,80)	-8.5 cells/µL Standard Deviation 399.48	15.2 cells/µL Standard Deviation 320.98	-10.1 cells/µL Standard Deviation 366.44	—	—

SECONDARY outcome

Timeframe: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48

Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.

Surface expression of CD8 was assessed by FACS analysis as a marker of cytotoxic T lymphocyte count. The normal range of CD8+ T cells was defined as 220-1129 cells/µL.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=127 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=114 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=91 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Peripheral CD8+ T Cell Count in Cells/µL BL Predose (n=127,110,90)	361.8 cells/µL Standard Deviation 231.86	352.6 cells/µL Standard Deviation 228.43	364.9 cells/µL Standard Deviation 181.22	—	—
Peripheral CD8+ T Cell Count in Cells/µL BL Postdose (n=118,109,85)	106.8 cells/µL Standard Deviation 70.64	118.6 cells/µL Standard Deviation 104.11	98.1 cells/µL Standard Deviation 70.68	—	—
Peripheral CD8+ T Cell Count in Cells/µL Day 15 Predose (n=127,114,87)	358.8 cells/µL Standard Deviation 196.37	360.9 cells/µL Standard Deviation 232.26	359.7 cells/µL Standard Deviation 174.12	—	—
Peripheral CD8+ T Cell Count in Cells/µL Day 15 Postdose (n=121,108,89)	134.0 cells/µL Standard Deviation 79.79	152.6 cells/µL Standard Deviation 130.11	145.6 cells/µL Standard Deviation 95.64	—	—
Peripheral CD8+ T Cell Count in Cells/µL Wk 4 (n=127,111,87)	348.4 cells/µL Standard Deviation 202.67	330.7 cells/µL Standard Deviation 197.94	341.9 cells/µL Standard Deviation 164.61	—	—
Peripheral CD8+ T Cell Count in Cells/µL Wk 8 (n=126,111,90)	357.3 cells/µL Standard Deviation 199.77	367.9 cells/µL Standard Deviation 239.39	342.3 cells/µL Standard Deviation 159.31	—	—
Peripheral CD8+ T Cell Count in Cells/µL Wk 16 (n=122,112,91)	365.1 cells/µL Standard Deviation 220.35	377.8 cells/µL Standard Deviation 227.32	344.2 cells/µL Standard Deviation 169.67	—	—
Peripheral CD8+ T Cell Count in Cells/µL Wk 24 (n=113,107,85)	359.1 cells/µL Standard Deviation 189.24	382.0 cells/µL Standard Deviation 241.73	363.3 cells/µL Standard Deviation 184.04	—	—
Peripheral CD8+ T Cell Count in Cells/µL Wk 28 (n=120,101,86)	359.9 cells/µL Standard Deviation 208.91	353.7 cells/µL Standard Deviation 221.13	357.3 cells/µL Standard Deviation 182.90	—	—
Peripheral CD8+ T Cell Count in Cells/µL Wk 32 (n=122,107,88)	372.3 cells/µL Standard Deviation 213.84	372.7 cells/µL Standard Deviation 211.86	359.9 cells/µL Standard Deviation 169.32	—	—
Peripheral CD8+ T Cell Count in Cells/µL Wk 40 (n=118,103,84)	367.8 cells/µL Standard Deviation 215.21	386.7 cells/µL Standard Deviation 260.49	356.7 cells/µL Standard Deviation 166.19	—	—
Peripheral CD8+ T Cell Count in Cells/µL Wk 48 (n=114,103,83)	365.9 cells/µL Standard Deviation 218.78	357.8 cells/µL Standard Deviation 210.51	355.5 cells/µL Standard Deviation 178.67	—	—

SECONDARY outcome

Timeframe: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48

Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.

Surface expression of CD8 was assessed by FACS analysis as a marker of cytotoxic T lymphocyte count. The normal range of CD8+ T cells was defined as 220-1129 cells/µL.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=122 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=107 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=88 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Change From BL in Peripheral CD8+ Cell Count BL Postdose (n=115,106,82)	-256.2 cells/µL Standard Deviation 190.92	-229.0 cells/µL Standard Deviation 183.97	-262.3 cells/µL Standard Deviation 148.57	—	—
Change From BL in Peripheral CD8+ Cell Count Day 15 Predose (n=122,107,84)	-1.5 cells/µL Standard Deviation 140.66	2.6 cells/µL Standard Deviation 167.12	-5.0 cells/µL Standard Deviation 122.68	—	—
Change From BL in Peripheral CD8+ Cell Count Day 15 Postdose (n=116,102,86)	-222.4 cells/µL Standard Deviation 180.50	-201.4 cells/µL Standard Deviation 176.30	-215.5 cells/µL Standard Deviation 140.77	—	—
Change From BL in Peripheral CD8+ Cell Count Wk 4 (n=122,105,84)	-17.3 cells/µL Standard Deviation 127.14	-18.0 cells/µL Standard Deviation 128.02	-17.6 cells/µL Standard Deviation 124.74	—	—
Change From BL in Peripheral CD8+ Cell Count Wk 8 (n=121,105,87)	-6.6 cells/µL Standard Deviation 157.14	16.3 cells/µL Standard Deviation 148.14	-21.3 cells/µL Standard Deviation 101.94	—	—
Change From BL in Peripheral CD8+ Cell Count Wk 16 (n=117,105,88)	-1.2 cells/µL Standard Deviation 176.58	18.0 cells/µL Standard Deviation 117.74	-16.3 cells/µL Standard Deviation 114.90	—	—
Change From BL in Peripheral CD8+ Cell Count Wk 24 (n=109,100,82)	2.1 cells/µL Standard Deviation 150.31	14.3 cells/µL Standard Deviation 160.58	0.4 cells/µL Standard Deviation 130.37	—	—
Change From BL in Peripheral CD8+ Cell Count Wk 28 (n=115,94,84)	-3.5 cells/µL Standard Deviation 183.31	7.2 cells/µL Standard Deviation 139.69	-7.3 cells/µL Standard Deviation 130.24	—	—
Change From BL in Peripheral CD8+ Cell Count Wk 32 (n=116,99,85)	3.6 cells/µL Standard Deviation 163.20	11.6 cells/µL Standard Deviation 144.92	-8.6 cells/µL Standard Deviation 129.83	—	—
Change From BL in Peripheral CD8+ Cell Count Wk 40 (n=113,96,81)	11.9 cells/µL Standard Deviation 174.03	22.3 cells/µL Standard Deviation 197.32	-8.5 cells/µL Standard Deviation 112.07	—	—
Change From BL in Peripheral CD8+ Cell Count Wk 48 (n=110,96,80)	-6.1 cells/µL Standard Deviation 168.67	2.2 cells/µL Standard Deviation 143.87	-10.1 cells/µL Standard Deviation 150.14	—	—

SECONDARY outcome

Timeframe: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48

Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.

Simultaneous surface expression of CD16 and CD56 was assessed by FACS analysis as a marker of NK cell count.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=127 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=114 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=91 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL BL Predose (n=127,110,90)	172.3 cells/µL Standard Deviation 102.58	173.5 cells/µL Standard Deviation 100.55	174.3 cells/µL Standard Deviation 99.82	—	—
Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL BL Postdose (n=118,109,85)	99.2 cells/µL Standard Deviation 51.46	111.7 cells/µL Standard Deviation 56.35	92.4 cells/µL Standard Deviation 52.96	—	—
Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL Day 15 Predose (n=127,114,87)	175.7 cells/µL Standard Deviation 95.76	180.6 cells/µL Standard Deviation 114.27	168.8 cells/µL Standard Deviation 84.38	—	—
Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL Day 15 Postdose (n=121,108,89)	170.8 cells/µL Standard Deviation 100.96	181.8 cells/µL Standard Deviation 103.36	173.7 cells/µL Standard Deviation 96.23	—	—
Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL Wk 4 (n=127,111,87)	180.1 cells/µL Standard Deviation 103.51	182.0 cells/µL Standard Deviation 110.95	173.2 cells/µL Standard Deviation 94.15	—	—
Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL Wk 8 (n=126,111,90)	197.7 cells/µL Standard Deviation 107.89	189.3 cells/µL Standard Deviation 105.93	177.8 cells/µL Standard Deviation 92.23	—	—
Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL Wk 16 (n=122,112,91)	201.7 cells/µL Standard Deviation 115.66	193.8 cells/µL Standard Deviation 120.85	184.1 cells/µL Standard Deviation 87.33	—	—
Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL Wk 24 (n=113,107,85)	188.8 cells/µL Standard Deviation 93.43	201.8 cells/µL Standard Deviation 120.24	182.6 cells/µL Standard Deviation 99.76	—	—
Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL Wk 28 (n=120,101,86)	203.4 cells/µL Standard Deviation 120.70	200.1 cells/µL Standard Deviation 119.07	200.8 cells/µL Standard Deviation 114.49	—	—
Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL Wk 32 (n=122,107,88)	212.5 cells/µL Standard Deviation 127.77	219.0 cells/µL Standard Deviation 130.92	193.8 cells/µL Standard Deviation 93.87	—	—
Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL Wk 40 (n=118,103,84)	222.4 cells/µL Standard Deviation 145.80	213.0 cells/µL Standard Deviation 127.08	214.8 cells/µL Standard Deviation 122.52	—	—
Peripheral CD16+56+ Natural Killer (NK) Cell Count in Cells/µL Wk 48 (n=114,103,83)	208.4 cells/µL Standard Deviation 117.23	216.2 cells/µL Standard Deviation 128.45	212.2 cells/µL Standard Deviation 111.62	—	—

SECONDARY outcome

Timeframe: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48

Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.

Simultaneous surface expression of CD16 and CD56 was assessed by FACS analysis as a marker of NK cell count.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=122 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=107 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=88 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Change From BL in Peripheral CD16+56+ Cell Count BL Postdose (n=115,106,82)	-72.2 cells/µL Standard Deviation 92.33	-60.5 cells/µL Standard Deviation 93.63	-83.2 cells/µL Standard Deviation 84.98	—	—
Change From BL in Peripheral CD16+56+ Cell Count Day 15 Predose (n=122,107,84)	4.0 cells/µL Standard Deviation 72.79	4.5 cells/µL Standard Deviation 74.48	-1.4 cells/µL Standard Deviation 64.87	—	—
Change From BL in Peripheral CD16+56+ Cell Count Day 15 Postdose (n=116,102,86)	-0.2 cells/µL Standard Deviation 91.95	8.8 cells/µL Standard Deviation 104.11	-2.7 cells/µL Standard Deviation 84.49	—	—
Change From BL in Peripheral CD16+56+ Cell Count Wk 4 (n=122,105,84)	8.8 cells/µL Standard Deviation 81.85	15.6 cells/µL Standard Deviation 80.56	3.4 cells/µL Standard Deviation 79.93	—	—
Change From BL in Peripheral CD16+56+ Cell Count Wk 8 (n=121,105,87)	25.7 cells/µL Standard Deviation 88.56	15.1 cells/µL Standard Deviation 82.02	4.8 cells/µL Standard Deviation 61.94	—	—
Change From BL in Peripheral CD16+56+ Cell Count Wk 16 (n=117,105,88)	29.1 cells/µL Standard Deviation 96.16	17.2 cells/µL Standard Deviation 73.16	12.3 cells/µL Standard Deviation 80.04	—	—
Change From BL in Peripheral CD16+56+ Cell Count Wk 24 (n=109,100,82)	13.2 cells/µL Standard Deviation 89.73	28.8 cells/µL Standard Deviation 86.61	8.0 cells/µL Standard Deviation 76.78	—	—
Change From BL in Peripheral CD16+56+ Cell Count Wk 28 (n=115,94,84)	30.3 cells/µL Standard Deviation 103.95	29.5 cells/µL Standard Deviation 95.65	24.8 cells/µL Standard Deviation 81.95	—	—
Change From BL in Peripheral CD16+56+ Cell Count Wk 32 (n=116,99,85)	41.0 cells/µL Standard Deviation 109.60	39.8 cells/µL Standard Deviation 90.37	19.0 cells/µL Standard Deviation 82.51	—	—
Change From BL in Peripheral CD16+56+ Cell Count Wk 40 (n=113,96,81)	53.6 cells/µL Standard Deviation 125.06	38.8 cells/µL Standard Deviation 101.55	40.6 cells/µL Standard Deviation 90.44	—	—
Change From BL in Peripheral CD16+56+ Cell Count Wk 48 (n=110,96,80)	34.7 cells/µL Standard Deviation 94.33	39.8 cells/µL Standard Deviation 87.49	38.9 cells/µL Standard Deviation 85.59	—	—

SECONDARY outcome

Timeframe: BL, Weeks 24 and 48

Population: ITT-M2 population, n=number of participants assessed for the given parameter at the specified timepoint.

The LLNs for total Ig, IgA, IgG, and IgM were defined as 6.75 grams per liter (g/L), 0.70 g/L, 65 g/L, and 0.40 g/L, respectively.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=131 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=113 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=93 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate n=6 Participants Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate n=25 Participants Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN BL, total Ig <LLN (n=131,113,93,6,25)	0.8 percentage of participants	0.9 percentage of participants	1.1 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN BL, total IgA <LLN (n=131,113,93,6,25)	0.8 percentage of participants	0.9 percentage of participants	2.2 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN BL, total IgG <LLN (n=131,113,93,6,25)	2.3 percentage of participants	0.9 percentage of participants	2.2 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN BL, total IgM <LLN (n=131,113,93,6,25)	0.8 percentage of participants	0.0 percentage of participants	1.1 percentage of participants	0.0 percentage of participants	4.0 percentage of participants
Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN Wk 24, total Ig <LLN (n=117,109,83,4,24)	0.9 percentage of participants	0.9 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN Wk 24, total IgA <LLN (n=117,109,83,4,24)	0.0 percentage of participants	0.9 percentage of participants	1.2 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN Wk 24, total IgG <LLN (n=117,109,83,4,24)	0.9 percentage of participants	0.9 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN Wk 24, total IgM <LLN (n=117,109,83,4,24)	7.7 percentage of participants	7.3 percentage of participants	6.0 percentage of participants	0.0 percentage of participants	16.7 percentage of participants
Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN Wk 48, total Ig <LLN (n=117,105,89,4,22)	0.9 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	4.5 percentage of participants
Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN Wk 48, total IgA <LLN (n=117,105,89,4,22)	1.7 percentage of participants	1.0 percentage of participants	2.2 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN Wk 48, total IgG <LLN (n=117,105,89,4,22)	1.7 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	4.5 percentage of participants
Percentage of Participants With Total Immunoglobin (Ig), IgA, IgG, and IgM Results Below the LLN Wk 48, total IgM <LLN (n=117,105,89,4,22)	13.7 percentage of participants	13.3 percentage of participants	10.1 percentage of participants	0.0 percentage of participants	18.2 percentage of participants

SECONDARY outcome

Timeframe: BL, Weeks 8, 24, and 48

Population: RF seropositive participants from the ITT-M2 population, n=number of participants assessed for the given parameter at the specified timepoint.

Percentage of participants who were RF seropositive at BL who became RF seronegative over the course of the study. RF seropositive status was defined as RF ≥ 20 international units (IU) per mL. RF seronegative status was defined as RF < 20 IU/mL.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=93 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=84 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=60 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Percentage of Participants Who Were Rheumatoid Factor (RF) - Seronegative Wk 8 (n=93,84,60)	9.7 percentage of participants	9.5 percentage of participants	5.0 percentage of participants	—	—
Percentage of Participants Who Were Rheumatoid Factor (RF) - Seronegative Wk 24 (n=83,79,56)	22.9 percentage of participants	21.5 percentage of participants	16.1 percentage of participants	—	—
Percentage of Participants Who Were Rheumatoid Factor (RF) - Seronegative Wk 48 (n=85,78,60)	30.6 percentage of participants	30.8 percentage of participants	23.3 percentage of participants	—	—

SECONDARY outcome

Timeframe: BL

Population: SAP. 3, 3, and 2 participants were not analyzed for this outcome measure from the Low Dose, Escalated Dose, and High Dose, groups, respectively.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=131 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=116 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=91 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate n=6 Participants Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate n=25 Participants Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Anti-Cyclic Citrullinated Peptide (CCP) Antibody Titers at BL in Units Per mL (U/mL)	205.39 U/mL Standard Deviation 374.203	179.01 U/mL Standard Deviation 255.251	263.61 U/mL Standard Deviation 477.554	184.77 U/mL Standard Deviation 304.169	310.94 U/mL Standard Deviation 334.849

SECONDARY outcome

Timeframe: Weeks 8, 24, and 48

Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=127 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=112 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=87 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate n=6 Participants Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate n=24 Participants Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Change From BL in Anti-CCP Antibody Titers in U/mL Wk 8 (n=127,112,85,6,24)	-42.97 U/mL Standard Deviation 94.873	-46.84 U/mL Standard Deviation 140.589	-70.39 U/mL Standard Deviation 265.694	-33.80 U/mL Standard Deviation 58.443	-18.67 U/mL Standard Deviation 54.228
Change From BL in Anti-CCP Antibody Titers in U/mL Wk 24 (n=117,107,82,4,24)	-68.23 U/mL Standard Deviation 158.951	-56.76 U/mL Standard Deviation 144.256	-72.96 U/mL Standard Deviation 219.466	-70.33 U/mL Standard Deviation 149.881	-64.32 U/mL Standard Deviation 89.763
Change From BL in Anti-CCP Antibody Titers in U/mL Wk 48 (n=116,102,87,4,22)	-72.99 U/mL Standard Deviation 151.086	-82.51 U/mL Standard Deviation 223.577	-127.21 U/mL Standard Deviation 307.981	-28.98 U/mL Standard Deviation 42.881	-81.57 U/mL Standard Deviation 167.012

SECONDARY outcome

Timeframe: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48

Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint

The LLN for C3 protein was defined as <0.9 grams per liter (g/L).

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=127 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=115 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=88 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN BL Predose (n=127,108,86)	3.1 percentage of participants	0.9 percentage of participants	1.2 percentage of participants	—	—
Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN BL Postdose (n=122,109,87)	3.3 percentage of participants	2.8 percentage of participants	5.7 percentage of participants	—	—
Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN Day 15 Predose (n=124,115,84)	2.4 percentage of participants	0.9 percentage of participants	2.4 percentage of participants	—	—
Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN Day 15 Postdose (n=122,113,82)	0.8 percentage of participants	0.0 percentage of participants	2.4 percentage of participants	—	—
Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN Week 4 (n=121,113,83)	3.3 percentage of participants	0.0 percentage of participants	1.2 percentage of participants	—	—
Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN BL Pre Retreatment (n=121,105,88)	6.6 percentage of participants	1.9 percentage of participants	3.4 percentage of participants	—	—
Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN BL Post Retreatment (n=118,103,82)	4.2 percentage of participants	2.9 percentage of participants	7.3 percentage of participants	—	—
Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN Day 15 Pre Retreatment (n=120,105,86)	6.7 percentage of participants	1.9 percentage of participants	7.0 percentage of participants	—	—
Percentage of Participants With Complement Component 3 (C3) Protein Level ≤ LLN Day 15 Post Retreatment (n=119,107,88)	5.9 percentage of participants	4.7 percentage of participants	8.0 percentage of participants	—	—

SECONDARY outcome

Timeframe: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48

Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint

The LLN of C3 protein was defined as <0.9 g/L.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=120 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=105 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=84 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Change From BL in Complement C3 Protein Level in g/L BL Postdose (n=119,102,84)	-0.0469 g/L Standard Deviation 0.17761	-0.0563 g/L Standard Deviation 0.16277	-0.0802 g/L Standard Deviation 0.12774	—	—
Change From BL in Complement C3 Protein Level in g/L Day 15 Predose (n=120,105,80)	-0.0423 g/L Standard Deviation 0.20915	-0.0143 g/L Standard Deviation 0.17514	-0.0773 g/L Standard Deviation 0.17876	—	—
Change From BL in Complement C3 Protein Level in g/L Day 15 Postdose (n=118,104,79)	-0.0413 g/L Standard Deviation 0.18365	-0.0235 g/L Standard Deviation 0.19255	-0.1094 g/L Standard Deviation 0.21860	—	—
Change From BL in Complement C3 Protein Level in g/L Wk 4 (n=118,105,78)	-0.0137 g/L Standard Deviation 0.22743	0.0279 g/L Standard Deviation 0.20724	-0.0596 g/L Standard Deviation 0.18186	—	—
Change From BL in Complement C3 Protein Level in g/L BL Pre Retreatment (n=115,98,83)	-0.0621 g/L Standard Deviation 0.21365	-0.0225 g/L Standard Deviation 0.20578	-0.0864 g/L Standard Deviation 0.19814	—	—
Change From BL in Complement C3 Protein Level in g/L BL Post Retreatment (n=113,97,78)	-0.0889 g/L Standard Deviation 0.21974	-0.0673 g/L Standard Deviation 0.21150	-0.1395 g/L Standard Deviation 0.21823	—	—
Change From BL in Complement C3 Protein Level in g/L Day 15 Pre Retreatment (n=115,97,81)	-0.0953 g/L Standard Deviation 0.20329	-0.0580 g/L Standard Deviation 0.26221	-0.1374 g/L Standard Deviation 0.19296	—	—
Change From BL in Complement C3 Protein Level in g/L Day 15 Post Retreatment (n=113,99,82)	-0.1048 g/L Standard Deviation 0.20255	-0.0979 g/L Standard Deviation 0.23505	-0.1533 g/L Standard Deviation 0.21412	—	—

SECONDARY outcome

Timeframe: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48

Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=27 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=21 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=22 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Change From BL in Activated Complement Component 3a (C3a) Protein Level in g/L BL Postdose (n=27,21,22)	-326.9 g/L Standard Deviation 3990.88	-92.8 g/L Standard Deviation 836.55	1319.9 g/L Standard Deviation 5104.05	—	—
Change From BL in Activated Complement Component 3a (C3a) Protein Level in g/L Day 15 Predose (n=18,10,14)	-1176.8 g/L Standard Deviation 4494.98	-17.1 g/L Standard Deviation 389.94	1054.1 g/L Standard Deviation 5409.76	—	—
Change From BL in Activated Complement Component 3a (C3a) Protein Level in g/L Day 15 Postdose (n=18,10,14)	-1117.7 g/L Standard Deviation 4347.64	-285.4 g/L Standard Deviation 403.44	-164.9 g/L Standard Deviation 740.91	—	—
Change From BL in Activated Complement Component 3a (C3a) Protein Level in g/L Wk 4 (n=14,9,11)	103.9 g/L Standard Deviation 749.79	-124.2 g/L Standard Deviation 921.23	-142.4 g/L Standard Deviation 504.95	—	—

SECONDARY outcome

Timeframe: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48

Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint

The LLN of C4 protein was defined as < 0.1 g/L.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=127 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=115 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=88 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN BL Predose (n=127,108,86)	2.4 percentage of participants	0.0 percentage of participants	1.2 percentage of participants	—	—
Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN BL Postdose (n=122,109,87)	4.9 percentage of participants	0.9 percentage of participants	2.3 percentage of participants	—	—
Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN Day 15 Predose (n=124,115,83)	2.4 percentage of participants	0.0 percentage of participants	2.4 percentage of participants	—	—
Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN Day 15 Postdose (n=121,113,81)	2.5 percentage of participants	0.0 percentage of participants	1.2 percentage of participants	—	—
Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN Wk 4 (n=121,111,81)	1.7 percentage of participants	0.0 percentage of participants	2.5 percentage of participants	—	—
Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN BL Pre Retreatment (n=121,105,88)	1.7 percentage of participants	1.0 percentage of participants	1.1 percentage of participants	—	—
Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN BL Post Retreatment (n=118,103,81)	1.7 percentage of participants	1.0 percentage of participants	1.2 percentage of participants	—	—
Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN Day 15 Pre Retreatment (n=120,105,86)	1.7 percentage of participants	0.0 percentage of participants	1.2 percentage of participants	—	—
Percentage of Participants With Complement Component 4 (C4) Protein Level ≤ LLN Day 15 Post Retreatment (n=119,107,88)	2.5 percentage of participants	0.9 percentage of participants	1.1 percentage of participants	—	—

SECONDARY outcome

Timeframe: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48

Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=120 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=105 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=84 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Change From BL in Complement C4 Protein Level in g/L BL Pre Retreatment (n=115,98,83)	0.0046 g/L Standard Deviation 0.06671	0.0214 g/L Standard Deviation 0.06848	0.0128 g/L Standard Deviation 0.12884	—	—
Change From BL in Complement C4 Protein Level in g/L BL Postdose (n=119,102,84)	-0.0187 g/L Standard Deviation 0.04950	-0.0170 g/L Standard Deviation 0.04048	-0.0220 g/L Standard Deviation 0.02710	—	—
Change From BL in Complement C4 Protein Level in g/L Day 15 Predose (n=120,105,80)	-0.0139 g/L Standard Deviation 0.06109	-0.0089 g/L Standard Deviation 0.04479	-0.0230 g/L Standard Deviation 0.04330	—	—
Change From BL in Complement C4 Protein Level in g/L Day 15 Postdose (n=117,104,79)	-0.0126 g/L Standard Deviation 0.05330	-0.0071 g/L Standard Deviation 0.04819	-0.0320 g/L Standard Deviation 0.04947	—	—
Change From BL in Complement C4 Protein Level in g/L Wk 4 (n=118,104,78)	0.0020 g/L Standard Deviation 0.06441	0.0069 g/L Standard Deviation 0.05476	-0.0020 g/L Standard Deviation 0.08212	—	—
Change From BL in Complement C4 Protein Level in g/L BL Post Retreatment (n=113,97,77)	-0.0017 g/L Standard Deviation 0.05998	0.0064 g/L Standard Deviation 0.05432	-0.0068 g/L Standard Deviation 0.05746	—	—
Change From BL in Complement C4 Protein Level in g/L Day 15 Pre Retreatment (n=115,97,81)	-0.0049 g/L Standard Deviation 0.06120	0.0138 g/L Standard Deviation 0.12093	-0.0142 g/L Standard Deviation 0.05015	—	—
Change From BL in Complement C4 Protein Level in g/L Day 15 Post Retreatment (n=113,99,82)	-0.0079 g/L Standard Deviation 0.06431	-0.0014 g/L Standard Deviation 0.05706	-0.0168 g/L Standard Deviation 0.05079	—	—

SECONDARY outcome

Timeframe: BL, Day 15, Weeks 4, 8, 16, 24, 28, 32, 40, and 48

Population: SAP, n = number of participants assessed for the given parameter at the specified timepoint

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=26 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=21 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=22 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Change From BL in Activated Complement Component 4a (C4a) Protein Level in g/L BL Postdose (n=26,21,22)	-1424.3 g/L Standard Deviation 3801.86	-480.1 g/L Standard Deviation 3137.12	-3749.1 g/L Standard Deviation 13498.79	—	—
Change From BL in Activated Complement Component 4a (C4a) Protein Level in g/L Day 15 Predose (n=18,10,14)	-971.3 g/L Standard Deviation 3149.08	3004.9 g/L Standard Deviation 10300.68	3.5 g/L Standard Deviation 1832.62	—	—
Change From BL in Activated Complement Component 4a (C4a) Protein Level in g/L Day 15 Postdose (n=18,10,14)	-1885.3 g/L Standard Deviation 2458.08	-333.0 g/L Standard Deviation 706.11	-1011.1 g/L Standard Deviation 1574.01	—	—
Change From BL in Activated Complement Component 4a (C4a) Protein Level in g/L Wk 4 (n=14,8,10)	629.8 g/L Standard Deviation 5993.96	260.4 g/L Standard Deviation 1450.40	109.8 g/L Standard Deviation 1566.68	—	—

SECONDARY outcome

Timeframe: BL, Weeks 24 and 48

Population: SAP, n=number of participants assessed for the given parameter at the specified timepoint.

A participant was defined as being HACA positive if the HACA serum level was ≥ 5 relative units (RU) per mL and the physician comment read that participant was "immunodepletable with rituximab".

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=131 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=115 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=91 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate n=6 Participants Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate n=25 Participants Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers Wk 48 (n=115,104,87,4,22)	4.3 percentage of participants	1.0 percentage of participants	2.3 percentage of participants	25.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers BL (n=131,115,91,6,25)	0.0 percentage of participants	0.9 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Positive Human Anti-Chimeric Antibody (HACA) Titers Wk 24 (n=118,109,86,4,24)	5.1 percentage of participants	7.3 percentage of participants	2.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: BL, Weeks 24 and 48

Population: SAP, n=number of participants assessed for the given parameter at the specified timepoint.

ANA titers were obtained by the following serum dilution schema: negative = negative, borderline = 1 diluted to (:) 40 or 1:80, and positive ≥ 1:160. The change categories were defined for the change from BL to Weeks 24 and 48 according to this schema. Negative to borderline was defined as any change from negative to borderline as no dilution is given for negative results. Negative to positive was defined as at least a two-fold positive change in dilution from BL. Borderline to negative was defined as any change from borderline to negative as no dilution is given for negative results. Borderline to positive was defined as at least a two-fold positive change in dilution from BL. Positive to borderline was defined as at least a two-fold negative change in dilution from BL. Positive to negative was defined as at least a two-fold negative change in dilution from BL. Unchanged was defined as any difference in dilution less than two-fold.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=113 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=107 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=86 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate n=4 Participants Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate n=24 Participants Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers Wk 24, Negative to Borderline (n=113,107,80,4,24)	7.1 percentage of participants	1.9 percentage of participants	7.5 percentage of participants	0.0 percentage of participants	4.2 percentage of participants
Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers Wk 24, Borderline to Negative (n=113,107,80,4,24)	14.2 percentage of participants	16.8 percentage of participants	11.3 percentage of participants	25.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers Wk 24, Borderline to Positive (n=113,107,80,4,24)	0.0 percentage of participants	0.9 percentage of participants	1.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers Wk 24, Positive to Borderline (n=113,107,80,4,24)	0.9 percentage of participants	0.0 percentage of participants	6.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers Wk 24, Positive to Negative (n=113,107,80,4,24)	0.0 percentage of participants	0.9 percentage of participants	1.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers Wk 24, Unchanged (n=113,107,80,4,24)	77.9 percentage of participants	79.4 percentage of participants	72.5 percentage of participants	75.0 percentage of participants	95.8 percentage of participants
Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers Wk 48, Negative to Borderline (n=112,102,86,4,22)	2.7 percentage of participants	2.0 percentage of participants	2.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers Wk 48, Borderline to Negative (n=112,102,86,4,22)	23.2 percentage of participants	24.5 percentage of participants	16.3 percentage of participants	50.0 percentage of participants	9.1 percentage of participants
Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers Wk 48, Borderline to Positive (n=112,102,86,4,22)	0.0 percentage of participants	1.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers Wk 48, Positive to Borderline (n=112,102,86,4,22)	5.4 percentage of participants	3.9 percentage of participants	7.0 percentage of participants	0.0 percentage of participants	4.5 percentage of participants
Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers Wk 48, Positive to Negative (n=112,102,86,4,22)	4.5 percentage of participants	2.0 percentage of participants	3.5 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With a Change From BL by Category in Anti-Nuclear Antibodies (ANA) Titers Wk 48, Unchanged (n=112,102,86,4,22)	64.3 percentage of participants	66.7 percentage of participants	70.9 percentage of participants	50.0 percentage of participants	86.4 percentage of participants

SECONDARY outcome

Timeframe: BL, Weeks 24 and 48

Population: SAP, n=number of participants assessed for the given parameter at the specified timepoint.

A positive titer result to recall antigens was defined as a serum antibody level equal to or above the following protective levels: tetanus toxoid ≥ 0.1 IU/mL, influenza A > 12 U/mL, influenza B > 12 U/mL, and streptococcus (S.) pneumococcus ≥ 1.0 mg/L.

Outcome measures

Measure	Rituximab Low Dose + Methotrexate n=131 Participants Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=115 Participants Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=91 Participants Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate n=6 Participants Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate n=25 Participants Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Percentage of Participants With Positive Recall Antigen Antibody Titers Rubella, Day 1 Predose (n=125,110,88,6,25)	94.4 percentage of participants	98.2 percentage of participants	89.8 percentage of participants	100.0 percentage of participants	92.0 percentage of participants
Percentage of Participants With Positive Recall Antigen Antibody Titers Rubella, Wk 24 (n=114,107,82,4,24)	93.9 percentage of participants	97.2 percentage of participants	90.2 percentage of participants	100.0 percentage of participants	91.7 percentage of participants
Percentage of Participants With Positive Recall Antigen Antibody Titers Rubella, Wk 48 (n=112,100,88,4,21)	94.6 percentage of participants	97.0 percentage of participants	89.8 percentage of participants	100.0 percentage of participants	95.2 percentage of participants
Percentage of Participants With Positive Recall Antigen Antibody Titers S. Pneumococcus, Day 1 Predose (n=130,114,91,6,25)	100.0 percentage of participants	100.0 percentage of participants	100.0 percentage of participants	100.0 percentage of participants	100.0 percentage of participants
Percentage of Participants With Positive Recall Antigen Antibody Titers S. Pneumococcus, Wk 24 (n=118,108,83,4,24)	100.0 percentage of participants	100.0 percentage of participants	100.0 percentage of participants	100.0 percentage of participants	100.0 percentage of participants
Percentage of Participants With Positive Recall Antigen Antibody Titers S. Pneumococcus, Wk 48 (n=116,105,89,4,22)	100.0 percentage of participants	100.0 percentage of participants	100.0 percentage of participants	100.0 percentage of participants	100.0 percentage of participants
Percentage of Participants With Positive Recall Antigen Antibody Titers Tetanus Toxoid, Day 1 Predose (n=131,115,91,6,25)	77.1 percentage of participants	70.4 percentage of participants	75.8 percentage of participants	66.7 percentage of participants	84.0 percentage of participants
Percentage of Participants With Positive Recall Antigen Antibody Titers Tetanus Toxoid, Wk 24 (n=118,107,83,4,24)	72.0 percentage of participants	69.2 percentage of participants	73.5 percentage of participants	75.0 percentage of participants	62.5 percentage of participants
Percentage of Participants With Positive Recall Antigen Antibody Titers Tetanus Toxoid, Wk 48 (n=118,105,89,4,22)	71.2 percentage of participants	66.7 percentage of participants	73.0 percentage of participants	75.0 percentage of participants	54.5 percentage of participants
Percentage of Participants With Positive Recall Antigen Antibody Titers Varicella, Day 1 Predose (n=129,114,88,6,25)	94.6 percentage of participants	94.7 percentage of participants	97.7 percentage of participants	100.0 percentage of participants	96.0 percentage of participants
Percentage of Participants With Positive Recall Antigen Antibody Titers Varicella, Wk 24 (n=114,105,79,4,23)	94.7 percentage of participants	94.3 percentage of participants	96.2 percentage of participants	100.0 percentage of participants	95.7 percentage of participants
Percentage of Participants With Positive Recall Antigen Antibody Titers Varicella, Wk 48 (n=114,101,87,4,22)	94.7 percentage of participants	94.1 percentage of participants	96.6 percentage of participants	100.0 percentage of participants	100.0 percentage of participants

Adverse Events

Rituximab Low Dose + Methotrexate

Serious events: 15 serious events

Other events: 120 other events

Deaths: 0 deaths

Rituximab Escalated Dose + Methotrexate

Serious events: 21 serious events

Other events: 103 other events

Deaths: 0 deaths

Rituximab High Dose + Methotrexate

Serious events: 16 serious events

Other events: 88 other events

Deaths: 0 deaths

Rituximab/Placebo + Methotrexate

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Rituximab Decreased Dose + Methotrexate

Serious events: 3 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Measure	Rituximab Low Dose + Methotrexate n=134 participants at risk Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=119 participants at risk Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=93 participants at risk Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate n=6 participants at risk Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate n=25 participants at risk Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Gastrointestinal disorders Abdominal pain	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Gastrointestinal disorders Diverticulum	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Gastrointestinal disorders Inguinal hernia	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Hepatobiliary disorders Cholelithiasis	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Nervous system disorders Intracranial aneurysm	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Nervous system disorders Sciatica	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.0% 1/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Nervous system disorders Tremor	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Eye disorders Ocular vascular disorder	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Renal and urinary disorders Renal colic	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Reproductive system and breast disorders Endometriosis	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Skin and subcutaneous tissue disorders Skin ulcer	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	1.5% 2/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.2% 5/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.7% 2/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Musculoskeletal and connective tissue disorders Back pain	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Musculoskeletal and connective tissue disorders Bunion	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Musculoskeletal and connective tissue disorders Intervertebral disc disorder	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Musculoskeletal and connective tissue disorders Osteoporotic fracture	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hodgkin's disease	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Morton's neuroma	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
General disorders Infusion related reaction	1.5% 2/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
General disorders Fatigue	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
General disorders Pyrexia	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Bronchopneumonia	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.0% 1/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Bronchitis	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Diverticulitis	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Gastroenteritis	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Lower respiratory tract infection	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Postoperative wound infection	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Pyelonephritis acute	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Respiratory tract infection	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Sepsis	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Cardiac disorders Myocardial infarction	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Cardiac disorders Acute myocardial infarction	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Cardiac disorders Atrial fibrillation	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.0% 1/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Cardiac disorders Cardiac valve disease	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Cardiac disorders Myocardial ischaemia	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Cardiac disorders Pericarditis	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Injury, poisoning and procedural complications Fall	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Injury, poisoning and procedural complications Device failure	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Injury, poisoning and procedural complications Joint dislocation	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.

Other adverse events

Measure	Rituximab Low Dose + Methotrexate n=134 participants at risk Participants received rituximab, 0.5 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab Escalated Dose + Methotrexate n=119 participants at risk Participants received rituximab, 0.5 g, IV, on Days 1 and 15 and 1.0 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab High Dose + Methotrexate n=93 participants at risk Participants received rituximab, 1.0 g, IV, on Days 1, 15, 168, and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose.	Rituximab/Placebo + Methotrexate n=6 participants at risk Participants received rituximab, 1.0 g, IV, on Days 1 and 15, and a placebo, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.	Rituximab Decreased Dose + Methotrexate n=25 participants at risk Participants received rituximab, 1.0 g, IV, on Days 1 and 15 and 0.5 g, IV, on Days 168 and 182. Participants also received methylprednisolone 100 mg, IV, by slow infusion, which was completed at least 30 minutes prior to each infusion of rituximab Days 1, 15, 168, and 182. Participants also received methotrexate 10-25 mg/mL, PO or parenterally, as prescribed by the treating physician and in accordance with the local label. Participants also received a stable dose of folate ≥ 5 mg/week given either as a single dose or as a divided weekly dose. This treatment group was not part of the planned analysis and was not analyzed for all outcomes measures since they did not receive the planned treatment.
Infections and infestations Upper respiratory tract infection	29.1% 39/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	31.1% 37/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	30.1% 28/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	24.0% 6/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Nasopharyngitis	23.1% 31/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	21.0% 25/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	29.0% 27/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	66.7% 4/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	28.0% 7/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Urinary tract infection	19.4% 26/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.8% 20/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	18.3% 17/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	8.0% 2/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Bronchitis	17.2% 23/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	11.8% 14/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	18.3% 17/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	20.0% 5/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Sinusitis	9.7% 13/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	13.4% 16/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	18.3% 17/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.0% 1/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Influenza	13.4% 18/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	9.2% 11/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	12.9% 12/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	8.0% 2/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Gastroenteritis	8.2% 11/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	11.8% 14/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	14.0% 13/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	33.3% 2/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	12.0% 3/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Pharyngitis	6.0% 8/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	5.9% 7/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	8.6% 8/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.0% 4/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Lower respiratory tract infection	6.0% 8/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	5.0% 6/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	3.2% 3/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	50.0% 3/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.0% 1/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Rhinitis	5.2% 7/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	7.6% 9/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	5.4% 5/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Oral herpes	2.2% 3/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	9.2% 11/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	5.4% 5/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Cystitis	4.5% 6/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	5.9% 7/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	5.4% 5/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Respiratory tract infection	3.7% 5/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	5.9% 7/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.3% 4/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.0% 1/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Localised infection	1.5% 2/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	2.5% 3/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	5.4% 5/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.0% 1/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Paronychia	1.5% 2/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	5.0% 6/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Pneumonia	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.3% 4/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	8.0% 2/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Tooth abscess	2.2% 3/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	2.5% 3/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Laryngitis	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.7% 2/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	8.0% 2/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Infections and infestations Hordeolum	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	32.1% 43/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	27.7% 33/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	32.3% 30/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	66.7% 4/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	28.0% 7/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Musculoskeletal and connective tissue disorders Back pain	11.2% 15/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	8.4% 10/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	10.8% 10/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	33.3% 2/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	8.2% 11/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	12.6% 15/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	5.4% 5/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Musculoskeletal and connective tissue disorders Osteoarthritis	7.5% 10/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	6.7% 8/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	3.2% 3/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	8.0% 2/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Musculoskeletal and connective tissue disorders Osteoporosis	6.0% 8/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	5.0% 6/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	5.4% 5/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Musculoskeletal and connective tissue disorders Tendonitis	2.2% 3/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	2.5% 3/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	7.5% 7/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.0% 1/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Musculoskeletal and connective tissue disorders Muscle spasms	3.7% 5/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	3.4% 4/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	3.2% 3/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.0% 1/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Musculoskeletal and connective tissue disorders Bursitis	2.2% 3/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	2.5% 3/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.3% 4/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.3% 4/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	33.3% 2/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Musculoskeletal and connective tissue disorders Neck pain	2.2% 3/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	5.4% 5/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	2.5% 3/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	8.0% 2/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.7% 2/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Injury, poisoning and procedural complications Infusion related reaction	43.3% 58/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	37.8% 45/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	38.7% 36/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	66.7% 4/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	36.0% 9/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Injury, poisoning and procedural complications Fall	11.2% 15/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	9.2% 11/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	10.8% 10/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.0% 1/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Injury, poisoning and procedural complications Contusion	1.5% 2/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	5.9% 7/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.3% 4/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.0% 1/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Injury, poisoning and procedural complications Procedural pain	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	5.0% 6/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	2.2% 2/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Injury, poisoning and procedural complications Soft tissue injury	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Gastrointestinal disorders Diarrhoea	13.4% 18/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	8.4% 10/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	10.8% 10/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	8.0% 2/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Gastrointestinal disorders Nausea	9.7% 13/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	5.0% 6/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	15.1% 14/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	12.0% 3/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Gastrointestinal disorders Dyspepsia	4.5% 6/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	9.2% 11/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	14.0% 13/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Gastrointestinal disorders Constipation	6.0% 8/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.2% 5/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	6.5% 6/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.0% 1/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Gastrointestinal disorders Abdominal pain upper	3.7% 5/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	5.9% 7/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	5.4% 5/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Gastrointestinal disorders Mouth ulceration	5.2% 7/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	3.4% 4/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.3% 4/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	8.0% 2/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Gastrointestinal disorders Gastrooesophageal reflux disease	3.0% 4/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.2% 5/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	6.5% 6/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.0% 1/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Gastrointestinal disorders Abdominal pain	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	2.5% 3/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	5.4% 5/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.0% 1/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Gastrointestinal disorders Gastritis	3.0% 4/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	2.5% 3/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	3.2% 3/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Gastrointestinal disorders Toothache	1.5% 2/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	2.2% 2/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Gastrointestinal disorders Colonic polyp	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Gastrointestinal disorders Gingival disorder	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Respiratory, thoracic and mediastinal disorders Cough	10.4% 14/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	12.6% 15/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	10.8% 10/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	8.0% 2/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.0% 8/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.7% 2/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	5.4% 5/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	12.0% 3/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	3.7% 5/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	5.0% 6/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	3.2% 3/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Nervous system disorders Headache	11.2% 15/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	8.4% 10/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	15.1% 14/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	8.0% 2/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Nervous system disorders Lethargy	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	8.0% 2/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Skin and subcutaneous tissue disorders Alopecia	5.2% 7/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	2.5% 3/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	5.4% 5/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Skin and subcutaneous tissue disorders Eczema	3.0% 4/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	3.4% 4/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.3% 4/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	8.0% 2/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Skin and subcutaneous tissue disorders Rash	1.5% 2/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	5.0% 6/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.3% 4/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.0% 1/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Skin and subcutaneous tissue disorders Dermatitis	3.0% 4/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.7% 2/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	2.2% 2/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.0% 1/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Skin and subcutaneous tissue disorders Dry skin	1.5% 2/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Vascular disorders Hypertension	9.7% 13/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	11.8% 14/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	15.1% 14/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	24.0% 6/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Psychiatric disorders Insomnia	8.2% 11/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	3.4% 4/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	8.0% 2/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Psychiatric disorders Depression	3.7% 5/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	7.6% 9/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.3% 4/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
General disorders Oedema peripheral	6.0% 8/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.2% 5/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	6.5% 6/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	8.0% 2/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Blood and lymphatic system disorders Anaemia	4.5% 6/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	2.5% 3/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.3% 4/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	8.0% 2/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Hepatobiliary disorders Hepatotoxicity	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.2% 5/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	3.2% 3/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.0% 4/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Metabolism and nutrition disorders Hypercholesterolaemia	3.7% 5/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.7% 2/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	3.2% 3/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	4.0% 1/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Immune system disorders Seasonal allergy	2.2% 3/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Immune system disorders Allergic oedema	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Cardiac disorders Myocardial ischaemia	0.75% 1/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.84% 1/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Cardiac disorders Bradycardia	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Eye disorders Eye pain	0.00% 0/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	1.1% 1/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	16.7% 1/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.
Nervous system disorders Dizziness	5.2% 7/134 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	6.7% 8/119 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	7.5% 7/93 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/6 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.	0.00% 0/25 • All adverse events (AEs) were collected from BL to Week 4 of Safety Follow-Up (SFU), after which only serious AEs (SAEs) were collected for the remainder of the SFU. SFU was done 4, 12, 24, 36 and 48 weeks after withdrawal. The safety analysis group included all randomized participants who received at least 1 infusion of study medication.

Additional Information

Medical Communications

Hoffman-LaRoche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER