Trial Outcomes & Findings for A Study to Evaluate Ocrelizumab Compared With Placebo in Patients With Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate Therapy (NCT NCT00673920)

NCT ID: NCT00673920

Last Updated: 2020-12-04

Results Overview

ACR20 response: greater than or equal to (≥) 20% improvement in tender or swollen joint counts and 20% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) participant assessment of disease activity, 3) Patient Assessment of Pain (visual analog scale \[VAS\]), 4) participant assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) erythrocyte sedimentation rate (ESR) at each visit.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 314 participants
• Primary outcome timeframe: Week 24
• Results posted on: 2020-12-04

Participant Flow

Screening was completed within 28 days prior to randomization. This may have been extended by an additional 56 days, up to a maximum of 84 days, if washout from the respective disease modifying anti-rheumatic drugs (DMARDs) or if immunization was required.

Participant milestones

Measure	Placebo Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)	Ocrelizumab 400mg Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.	Ocrelizumab 200mg Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.	Ocrelizumab 200mg/ Ocrelizumab 200mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 200mg/ Ocrelizumab 400mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 400mg/ Ocrelizumab 400mg Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 200mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 400mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Baseline up to Week 48 STARTED	64	117	133	0	0	0	0	0
Baseline up to Week 48 COMPLETED	60	114	126	0	0	0	0	0
Baseline up to Week 48 NOT COMPLETED	4	3	7	0	0	0	0	0
Week 24 to Week 48 STARTED	0	0	0	61	61	109	29	28
Week 24 to Week 48 COMPLETED	0	0	0	60	61	106	28	28
Week 24 to Week 48 NOT COMPLETED	0	0	0	1	0	3	1	0

Reasons for withdrawal

Measure	Placebo Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)	Ocrelizumab 400mg Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.	Ocrelizumab 200mg Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.	Ocrelizumab 200mg/ Ocrelizumab 200mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 200mg/ Ocrelizumab 400mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 400mg/ Ocrelizumab 400mg Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 200mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 400mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Baseline up to Week 48 Withdrew consent	1	0	2	0	0	0	0	0
Baseline up to Week 48 Refused treatment	1	0	0	0	0	0	0	0
Baseline up to Week 48 Insufficient therapeutic response	2	1	0	0	0	0	0	0
Baseline up to Week 48 Protocol Violation	0	0	1	0	0	0	0	0
Baseline up to Week 48 Violation of selection criteria at entry	0	0	1	0	0	0	0	0
Baseline up to Week 48 Administrative/Other	0	1	2	0	0	0	0	0
Baseline up to Week 48 Adverse event/intercurrent illness	0	1	1	0	0	0	0	0
Week 24 to Week 48 Adverse event/intercurrent illness	0	0	0	0	0	0	1	0
Week 24 to Week 48 Failure to return	0	0	0	0	0	1	0	0
Week 24 to Week 48 Insufficient therapeutic response	0	0	0	0	0	1	0	0
Week 24 to Week 48 Death	0	0	0	0	0	1	0	0
Week 24 to Week 48 Adminstrative/Other	0	0	0	1	0	0	0	0

Baseline Characteristics

A Study to Evaluate Ocrelizumab Compared With Placebo in Patients With Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate Therapy

Baseline characteristics by cohort

Measure	Placebo n=64 Participants Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)	Ocrelizumab 400mg n=117 Participants Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.	Ocrelizumab 200mg n=131 Participants Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.	Ocrelizumab 200mg/ Ocrelizumab 200mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 200mg/ Ocrelizumab 400mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 400mg/ Ocrelizumab 400mg Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 200mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 400mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Total n=312 Participants Total of all reporting groups
Age, Continuous	53.1 Years STANDARD_DEVIATION 11.45 • n=5 Participants	52.3 Years STANDARD_DEVIATION 11.14 • n=7 Participants	53.0 Years STANDARD_DEVIATION 11.15 • n=5 Participants	—	—	—	—	—	52.8 Years STANDARD_DEVIATION 11.2 • n=42 Participants
Sex: Female, Male Female	56 Participants n=5 Participants	93 Participants n=7 Participants	105 Participants n=5 Participants	—	—	—	—	—	254 Participants n=42 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	24 Participants n=7 Participants	26 Participants n=5 Participants	—	—	—	—	—	58 Participants n=42 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants	22 Participants n=7 Participants	24 Participants n=5 Participants	—	—	—	—	—	56 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	54 Participants n=5 Participants	95 Participants n=7 Participants	107 Participants n=5 Participants	—	—	—	—	—	256 Participants n=42 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	—	—	—	—	—	0 Participants n=42 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	—	—	—	—	—	8 Participants n=42 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	13 Participants n=7 Participants	10 Participants n=5 Participants	—	—	—	—	—	27 Participants n=42 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	—	—	—	—	—	0 Participants n=42 Participants
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants	9 Participants n=7 Participants	9 Participants n=5 Participants	—	—	—	—	—	27 Participants n=42 Participants
Race (NIH/OMB) White	44 Participants n=5 Participants	85 Participants n=7 Participants	99 Participants n=5 Participants	—	—	—	—	—	228 Participants n=42 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	—	—	—	—	—	0 Participants n=42 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants	—	—	—	—	—	22 Participants n=42 Participants

PRIMARY outcome

Timeframe: Week 24

Population: ITT Population (original randomization)

ACR20 response: greater than or equal to (≥) 20% improvement in tender or swollen joint counts and 20% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) participant assessment of disease activity, 3) Patient Assessment of Pain (visual analog scale [VAS]), 4) participant assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) erythrocyte sedimentation rate (ESR) at each visit.

Outcome measures

Measure	Placebo n=64 Participants Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)	Ocrelizumab 400mg n=117 Participants Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.	Ocrelizumab 200mg - Cycle 1 n=131 Participants Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.	Ocrelizumab 200mg/ Ocrelizumab 200mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 200mg/ Ocrelizumab 400mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 400mg/ Ocrelizumab 400mg Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 200mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 400mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Percentage of Participants With American College of Rheumatology (ACR) 20 Response	28.1 Percentage of Participants Interval 17.1 to 39.1	37.6 Percentage of Participants Interval 28.8 to 46.4	52.7 Percentage of Participants Interval 44.1 to 61.2	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT Population (original randomization)

The DAS28 was derived from assessments of erythrocyte sedimentation rate (ESR) measured in millimeters per hour (mm/h), tender joint count on 28 joints (TJC28), swollen joint count on 28 joints (SJC28), and Patient's Global Assessment of disease activity according to 100--millimeter (mm) Visual Analog Scale (VAS). DAS28 score was calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. DAS28 score could range from 0 to 10, where higher score represented higher disease activity. The change from Week 24 to Week 40 was averaged among all participants, where negative changes indicated an improvement in disease activity.

Outcome measures

Measure	Placebo n=64 Participants Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)	Ocrelizumab 400mg n=117 Participants Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.	Ocrelizumab 200mg - Cycle 1 n=131 Participants Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.	Ocrelizumab 200mg/ Ocrelizumab 200mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 200mg/ Ocrelizumab 400mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 400mg/ Ocrelizumab 400mg Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 200mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 400mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Remission (DAS28 < 2.6)	3.1 Percentage of Participants	4.3 Percentage of Participants	5.3 Percentage of Participants	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT Population (original randomization)

The DAS28 was derived from assessments of erythrocyte sedimentation rate (ESR) measured in millimeters per hour (mm/h), tender joint count on 28 joints (TJC28), swollen joint count on 28 joints (SJC28), and Patient's Global Assessment of disease activity according to 100--millimeter (mm) Visual Analog Scale (VAS). DAS28 score was calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. DAS28 score could range from 0 to 10, where higher score represented higher disease activity. The change from Week 24 to Week 40 was averaged among all participants, where negative changes indicated an improvement in disease activity. The change is the difference in adjusted mean change from baseline in DAS28 between ocrelizumab 400 x 1 and ocrelizumab 200 x 2 with placebo.

Outcome measures

Measure	Placebo n=49 Participants Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)	Ocrelizumab 400mg n=104 Participants Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.	Ocrelizumab 200mg - Cycle 1 n=119 Participants Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.	Ocrelizumab 200mg/ Ocrelizumab 200mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 200mg/ Ocrelizumab 400mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 400mg/ Ocrelizumab 400mg Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 200mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 400mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Change in DAS28 From Baseline	-0.79 Units on scale Standard Deviation 1.293	-1.60 Units on scale Standard Deviation 1.374	-1.67 Units on scale Standard Deviation 1.320	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT Population (original randomization)

Outcome measures

Measure	Placebo n=64 Participants Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)	Ocrelizumab 400mg n=117 Participants Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.	Ocrelizumab 200mg - Cycle 1 n=131 Participants Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.	Ocrelizumab 200mg/ Ocrelizumab 200mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 200mg/ Ocrelizumab 400mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 400mg/ Ocrelizumab 400mg Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 200mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 400mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders) Week 4 No Response	62.5 Percentage of Participants	62.4 Percentage of Participants	58.0 Percentage of Participants	—	—	—	—	—
European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders) Week 4 Moderate Response	37.5 Percentage of Participants	33.3 Percentage of Participants	38.9 Percentage of Participants	—	—	—	—	—
European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders) Week 4 Good Response	0 Percentage of Participants	4.3 Percentage of Participants	3.1 Percentage of Participants	—	—	—	—	—
European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders) Week 8 No Response	70.3 Percentage of Participants	52.1 Percentage of Participants	48.1 Percentage of Participants	—	—	—	—	—
European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders) Week 8 Moderate Response	28.1 Percentage of Participants	39.3 Percentage of Participants	42.0 Percentage of Participants	—	—	—	—	—
European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders) Week 8 Good Response	1.6 Percentage of Participants	8.5 Percentage of Participants	9.9 Percentage of Participants	—	—	—	—	—
European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders) Week 12 No Response	68.8 Percentage of Participants	41.9 Percentage of Participants	35.9 Percentage of Participants	—	—	—	—	—
European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders) Week 12 Moderate Response	29.7 Percentage of Participants	49.6 Percentage of Participants	54.2 Percentage of Participants	—	—	—	—	—
European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders) Week 12 Good Response	1.6 Percentage of Participants	11.1 Percentage of Participants	9.9 Percentage of Participants	—	—	—	—	—
European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders) Week 16 No Response	68.8 Percentage of Participants	39.3 Percentage of Participants	35.1 Percentage of Participants	—	—	—	—	—
European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders) Week 16 Moderate Response	29.7 Percentage of Participants	49.6 Percentage of Participants	47.3 Percentage of Participants	—	—	—	—	—
European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders) Week 16 Good Response	1.6 Percentage of Participants	11.1 Percentage of Participants	17.6 Percentage of Participants	—	—	—	—	—
European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders) Week 20 No Response	68.8 Percentage of Participants	41.0 Percentage of Participants	30.5 Percentage of Participants	—	—	—	—	—
European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders) Week 20 Moderate Response	26.6 Percentage of Participants	48.7 Percentage of Participants	51.1 Percentage of Participants	—	—	—	—	—
European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders) Week 20 Good Response	4.7 Percentage of Participants	10.3 Percentage of Participants	18.3 Percentage of Participants	—	—	—	—	—
European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders) Week 24 Good Response	4.7 Percentage of Participants	14.5 Percentage of Participants	13.7 Percentage of Participants	—	—	—	—	—
European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders) Week 24 No Response	73.4 Percentage of Participants	44.4 Percentage of Participants	38.9 Percentage of Participants	—	—	—	—	—
European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders) Week 24 Moderate Response	21.9 Percentage of Participants	41.0 Percentage of Participants	47.3 Percentage of Participants	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT Population (original randomization)

The ACR50 response at any time was defined as >/=50% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 50% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) Patient's global assessment of disease activity according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via HAQ-DI, and 5) Acute phase reactant (ESR in mm/h or CRP in mg/dL).

Outcome measures

Measure	Placebo n=64 Participants Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)	Ocrelizumab 400mg n=117 Participants Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.	Ocrelizumab 200mg - Cycle 1 n=131 Participants Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.	Ocrelizumab 200mg/ Ocrelizumab 200mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 200mg/ Ocrelizumab 400mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 400mg/ Ocrelizumab 400mg Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 200mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 400mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Percentage of Participants Achieving an ACR50 Response	7.8 Percentage of Participants	18.8 Percentage of Participants	30.5 Percentage of Participants	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT Population (original randomization)

The ACR70 response at any time was defined as >/=70% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 70% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) Patient's global assessment of disease activity according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via HAQ-DI, and 5) Acute phase reactant (ESR in mm/h or CRP in mg/dL).

Outcome measures

Measure	Placebo n=64 Participants Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)	Ocrelizumab 400mg n=117 Participants Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.	Ocrelizumab 200mg - Cycle 1 n=131 Participants Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.	Ocrelizumab 200mg/ Ocrelizumab 200mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 200mg/ Ocrelizumab 400mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 400mg/ Ocrelizumab 400mg Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 200mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 400mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Percentage of Participants Achieving an ACR70 Response	1.6 Percentage of Participants	6.8 Percentage of Participants	7.6 Percentage of Participants	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT Population (original randomization)

Change in the scores of the following parameters of ACR core set relative to respective baseline scores was measured: SJC (28 and 66 joints) and TJC (28 and 66 joints), patient's global assessment and physician's global assessment based on disease activity (both are expressed by VAS [0 = no disease activity to 100 = maximum disease activity]), HAQ (based on HAQ disability index [HAQDI]) which included 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities) rated on a 4-point scale (0=without any difficulty to 3=unable to do), where the sum of scores was divided by the number of domains with a score for a total possible score of 0 (best) to 3 (worst), pain assessment using a VAS ranging from score 0 (no pain) to 100 (unbearable pain).

Outcome measures

Measure	Placebo n=64 Participants Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)	Ocrelizumab 400mg n=117 Participants Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.	Ocrelizumab 200mg - Cycle 1 n=131 Participants Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.	Ocrelizumab 200mg/ Ocrelizumab 200mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 200mg/ Ocrelizumab 400mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 400mg/ Ocrelizumab 400mg Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 200mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 400mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Change From Baseline in the Individual Parameters of the ACR Core Set SJC	-4.6 Units on a scale	-7.5 Units on a scale	-8.7 Units on a scale	—	—	—	—	—
Change From Baseline in the Individual Parameters of the ACR Core Set TJC	-8.2 Units on a scale	-10.2 Units on a scale	-12.0 Units on a scale	—	—	—	—	—
Change From Baseline in the Individual Parameters of the ACR Core Set Patient's global assessment	-7.6 Units on a scale	-21.2 Units on a scale	-24.3 Units on a scale	—	—	—	—	—
Change From Baseline in the Individual Parameters of the ACR Core Set Physician's global assessment	-16.0 Units on a scale	-24.3 Units on a scale	-26.0 Units on a scale	—	—	—	—	—
Change From Baseline in the Individual Parameters of the ACR Core Set Patient's pain assessment	-8.0 Units on a scale	-17.2 Units on a scale	-21.0 Units on a scale	—	—	—	—	—
Change From Baseline in the Individual Parameters of the ACR Core Set HAQ-DI	-0.2 Units on a scale	-0.4 Units on a scale	-0.5 Units on a scale	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT Population (original randomization)

Outcome measures

Measure	Placebo n=64 Participants Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)	Ocrelizumab 400mg n=117 Participants Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.	Ocrelizumab 200mg - Cycle 1 n=131 Participants Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.	Ocrelizumab 200mg/ Ocrelizumab 200mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 200mg/ Ocrelizumab 400mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 400mg/ Ocrelizumab 400mg Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 200mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 400mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Change From Baseline in the Individual Parameters of the ACR Core Set: C-Reactive Protein (CRP) Concentration	-0.2 mg/dL	-1.0 mg/dL	-0.8 mg/dL	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT Population (original randomization)

Outcome measures

Measure	Placebo n=64 Participants Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)	Ocrelizumab 400mg n=117 Participants Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.	Ocrelizumab 200mg - Cycle 1 n=131 Participants Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.	Ocrelizumab 200mg/ Ocrelizumab 200mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 200mg/ Ocrelizumab 400mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 400mg/ Ocrelizumab 400mg Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 200mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 400mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Change From Baseline in the Individual Parameters of the ACR Core Set: Erythrocyte Sedimentation Rate (ESR)	-3.0 mm/hr	-14.2 mm/hr	-11.1 mm/hr	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT Population (original randomization)

Outcome measures

Measure	Placebo n=64 Participants Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)	Ocrelizumab 400mg n=117 Participants Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.	Ocrelizumab 200mg - Cycle 1 n=131 Participants Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.	Ocrelizumab 200mg/ Ocrelizumab 200mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 200mg/ Ocrelizumab 400mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 400mg/ Ocrelizumab 400mg Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 200mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 400mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Percentage of Participants With a Reduction of Greater Than or Equal to 0.25 Units in the HAQ-DI Score	37.5 Percentage of Participants Interval 25.6 to 49.4	55.6 Percentage of Participants Interval 46.6 to 64.6	58.8 Percentage of Participants Interval 50.3 to 67.2	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 24

Population: ITT Population (original randomization)

Improved, change > 5.42; Unchanged, -5.42 <= Change <= 5.42; Worsened, change < -5.42

Outcome measures

Measure	Placebo n=64 Participants Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)	Ocrelizumab 400mg n=117 Participants Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.	Ocrelizumab 200mg - Cycle 1 n=131 Participants Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.	Ocrelizumab 200mg/ Ocrelizumab 200mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 200mg/ Ocrelizumab 400mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 400mg/ Ocrelizumab 400mg Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 200mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 400mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Change in SF-36 Subscale and Summary Scores From Baseline Mental Component Summary Category Improved	42.0 Percentage of Participants	34.9 Percentage of Participants	36.6 Percentage of Participants	—	—	—	—	—
Change in SF-36 Subscale and Summary Scores From Baseline Mental Component Summary Category Unchanged	38.0 Percentage of Participants	50.0 Percentage of Participants	51.2 Percentage of Participants	—	—	—	—	—
Change in SF-36 Subscale and Summary Scores From Baseline Mental Component Summary Category Worsened	20.0 Percentage of Participants	15.1 Percentage of Participants	12.2 Percentage of Participants	—	—	—	—	—
Change in SF-36 Subscale and Summary Scores From Baseline Physical Component Improved	44.0 Percentage of Participants	45.3 Percentage of Participants	53.7 Percentage of Participants	—	—	—	—	—
Change in SF-36 Subscale and Summary Scores From Baseline Physical Component Unchanged	42.0 Percentage of Participants	51.9 Percentage of Participants	42.3 Percentage of Participants	—	—	—	—	—
Change in SF-36 Subscale and Summary Scores From Baseline Physical Component Worsened	14.0 Percentage of Participants	2.8 Percentage of Participants	4.1 Percentage of Participants	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 12, and 24

Population: ITT Population (original randomization)

The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participants fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). Clinically relevant improvement is defined as a greater than or equal to (≥)5-point change from Baseline.

Outcome measures

Measure	Placebo n=64 Participants Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)	Ocrelizumab 400mg n=117 Participants Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.	Ocrelizumab 200mg - Cycle 1 n=131 Participants Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.	Ocrelizumab 200mg/ Ocrelizumab 200mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 200mg/ Ocrelizumab 400mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 400mg/ Ocrelizumab 400mg Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 200mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 400mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Change in FACIT-F Fatigue Assessment From Baseline Week 4	28.94 Units on a scale Standard Deviation 11.371	28.60 Units on a scale Standard Deviation 11.231	30.71 Units on a scale Standard Deviation 11.136	—	—	—	—	—
Change in FACIT-F Fatigue Assessment From Baseline Baseline	25.13 Units on a scale Standard Deviation 10.616	25.33 Units on a scale Standard Deviation 11.313	24.74 Units on a scale Standard Deviation 11.161	—	—	—	—	—
Change in FACIT-F Fatigue Assessment From Baseline Week 12	28.42 Units on a scale Standard Deviation 12.015	32.09 Units on a scale Standard Deviation 12.368	33.09 Units on a scale Standard Deviation 10.903	—	—	—	—	—
Change in FACIT-F Fatigue Assessment From Baseline Week 24	28.47 Units on a scale Standard Deviation 12.406	31.38 Units on a scale Standard Deviation 11.346	33.18 Units on a scale Standard Deviation 11.011	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 48

Population: Study extension period included all participants who were re-randomized at Week 24.

ACR20 response: greater than or equal to (≥) 20% improvement in tender or swollen joint counts and 20% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) participant assessment of disease activity, 3) Patient Assessment of Pain (visual analog scale [VAS]), 4) participant assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) erythrocyte sedimentation rate (ESR) at each visit.

Outcome measures

Measure	Placebo Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)	Ocrelizumab 400mg Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.	Ocrelizumab 200mg - Cycle 1 Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.	Ocrelizumab 200mg/ Ocrelizumab 200mg n=61 Participants Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 200mg/ Ocrelizumab 400mg n=61 Participants Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 400mg/ Ocrelizumab 400mg n=109 Participants Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 200mg n=29 Participants Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 400mg n=28 Participants Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Percentage of Participants Achieving an ACR20 Response	—	—	—	59.0 Percentage of Participants	54.1 Percentage of Participants	56.9 Percentage of Participants	44.8 Percentage of Participants	42.9 Percentage of Participants

SECONDARY outcome

Timeframe: Week 48

Population: Study extension period included all participants who were re-randomized at Week 24.

The ACR50 response at any time was defined as >/=50% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 50% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) Patient's global assessment of disease activity according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via HAQ-DI, and 5) Acute phase reactant (ESR in mm/h or CRP in mg/dL).

Outcome measures

Measure	Placebo Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)	Ocrelizumab 400mg Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.	Ocrelizumab 200mg - Cycle 1 Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.	Ocrelizumab 200mg/ Ocrelizumab 200mg n=61 Participants Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 200mg/ Ocrelizumab 400mg n=61 Participants Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 400mg/ Ocrelizumab 400mg n=109 Participants Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 200mg n=29 Participants Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 400mg n=28 Participants Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Percentage of Participants Achieving an ACR50 Response	—	—	—	36.1 Percentage of Participants	27.9 Percentage of Participants	34.9 Percentage of Participants	20.7 Percentage of Participants	14.3 Percentage of Participants

SECONDARY outcome

Timeframe: Week 48

Population: Study extension period included all participants who were re-randomized at Week 24.

The ACR70 response at any time was defined as >/=70% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 70% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) Patient's global assessment of disease activity according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via HAQ-DI, and 5) Acute phase reactant (ESR in mm/h or CRP in mg/dL).

Outcome measures

Measure	Placebo Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)	Ocrelizumab 400mg Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.	Ocrelizumab 200mg - Cycle 1 Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.	Ocrelizumab 200mg/ Ocrelizumab 200mg n=61 Participants Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 200mg/ Ocrelizumab 400mg n=61 Participants Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 400mg/ Ocrelizumab 400mg n=109 Participants Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 200mg n=29 Participants Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 400mg n=28 Participants Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Percentage of Participants Achieving an ACR70 Response	—	—	—	19.7 Percentage of Participants	16.4 Percentage of Participants	19.3 Percentage of Participants	6.9 Percentage of Participants	7.1 Percentage of Participants

SECONDARY outcome

Timeframe: Week 48

Population: Study extension period included all participants who were re-randomized at Week 24.

Outcome measures

Measure	Placebo Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)	Ocrelizumab 400mg Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.	Ocrelizumab 200mg - Cycle 1 Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.	Ocrelizumab 200mg/ Ocrelizumab 200mg n=61 Participants Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 200mg/ Ocrelizumab 400mg n=61 Participants Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 400mg/ Ocrelizumab 400mg n=109 Participants Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 200mg n=29 Participants Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 400mg n=28 Participants Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Percentage of Participants Achieving DAS28 Remission (DAS28 < 2.6)	—	—	—	13.1 Percentage of Participants	3.3 Percentage of Participants	11.0 Percentage of Participants	6.9 Percentage of Participants	3.6 Percentage of Participants

SECONDARY outcome

Timeframe: Week 24, 48

Population: Placebo population was excluded from the analysis.

Outcome measures

Measure	Placebo n=120 Participants Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)	Ocrelizumab 400mg n=85 Participants Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.	Ocrelizumab 200mg - Cycle 1 n=107 Participants Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.	Ocrelizumab 200mg/ Ocrelizumab 200mg n=183 Participants Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 200mg/ Ocrelizumab 400mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 400mg/ Ocrelizumab 400mg Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 200mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 400mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Cmax: Maximum Observed Serum Concentration of Ocrelizumab Following First Infusion	73.1 μg/mL Standard Deviation 63.8	67.7 μg/mL Standard Deviation 27.0	133 μg/mL Standard Deviation 38.5	137 μg/mL Standard Deviation 45.4	—	—	—	—

SECONDARY outcome

Timeframe: Day 15 of Cycles 1 and 2

Population: Population included all participants who received second Ocrelizumab infusion.

Outcome measures

Measure	Placebo n=117 Participants Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)	Ocrelizumab 400mg n=83 Participants Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.	Ocrelizumab 200mg - Cycle 1 Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.	Ocrelizumab 200mg/ Ocrelizumab 200mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 200mg/ Ocrelizumab 400mg Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 400mg/ Ocrelizumab 400mg Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 200mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 400mg Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Csecond: Maximum Observed Serum Concentration of Ocrelizumab Following Second Infusion	71.7 μg/mL Standard Deviation 18.0	77.6 μg/mL Standard Deviation 27.4	—	—	—	—	—	—

Adverse Events

Placebo

Serious events: 5 serious events

Other events: 32 other events

Deaths: 0 deaths

Ocrelizumab 400mg

Serious events: 3 serious events

Other events: 59 other events

Deaths: 0 deaths

Ocrelizumab 200mg

Serious events: 2 serious events

Other events: 80 other events

Deaths: 0 deaths

Ocrelizumab 200mg/ Ocrelizumab 200mg

Serious events: 5 serious events

Other events: 46 other events

Deaths: 0 deaths

Ocrelizumab 200mg/ Ocrelizumab 400mg

Serious events: 5 serious events

Other events: 49 other events

Deaths: 0 deaths

Ocrelizumab 400mg/ Ocrelizumab 400mg

Serious events: 10 serious events

Other events: 86 other events

Deaths: 1 deaths

Placebo/ Ocrelizumab 200mg

Serious events: 3 serious events

Other events: 20 other events

Deaths: 0 deaths

Placebo/ Ocrelizumab 400mg

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=64 participants at risk Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)	Ocrelizumab 400mg n=117 participants at risk Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.	Ocrelizumab 200mg n=131 participants at risk Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.	Ocrelizumab 200mg/ Ocrelizumab 200mg n=61 participants at risk Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 200mg/ Ocrelizumab 400mg n=61 participants at risk Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 400mg/ Ocrelizumab 400mg n=109 participants at risk Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 200mg n=29 participants at risk Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 400mg n=28 participants at risk Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Infections and infestations BRONCHIECTASIS	3.1% 2/64 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	2.6% 3/117 • Number of events 3 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.76% 1/131 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	8.2% 5/61 • Number of events 5 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	8.2% 5/61 • Number of events 5 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	8.3% 9/109 • Number of events 9 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	10.3% 3/29 • Number of events 3 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Infections and infestations MYCOBACTERIUM ABSCESSUS INFECTION	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.85% 1/117 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/109 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	3.4% 1/29 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Infections and infestations URINARY TRACT INFECTION	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.76% 1/131 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	1.6% 1/61 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/109 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Gastrointestinal disorders COLITIS ULCERATIVE	1.6% 1/64 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/109 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	1.6% 1/64 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/109 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	3.4% 1/29 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Infections and infestations CELLULITIS	1.6% 1/64 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/109 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Infections and infestations PNEUMONIA	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.85% 1/117 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/109 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Infections and infestations PROSTATE INFECTION	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.85% 1/117 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.92% 1/109 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
General disorders INFLUENZA LIKE ILLNESS	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.76% 1/131 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	1.6% 1/61 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/109 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) UTERINE LEIOMYOMA	1.6% 1/64 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/109 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	3.4% 1/29 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Psychiatric disorders DEPRESSION	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.76% 1/131 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	1.6% 1/61 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/109 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Gastrointestinal disorders COLITIS	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	1.6% 1/61 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/109 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Gastrointestinal disorders COLITIS ISCHAEMIC	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	1.6% 1/61 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/109 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Gastrointestinal disorders DIVERTICULAR PERFORATION	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.92% 1/109 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Gastrointestinal disorders GASTROINTESTINAL HAEMORRHAGE	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.92% 1/109 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Gastrointestinal disorders PANCREATITIS	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.92% 1/109 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Infections and infestations ESCHERICHIA URINARY TRACT INFECTION	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.92% 1/109 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Infections and infestations PYELONEPHRITIS	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	1.6% 1/61 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/109 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BASAL CELL CARCINOMA	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	1.6% 1/61 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/109 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) MALIGNANT MELANOMA	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.92% 1/109 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) PROSTATE CANCER	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	1.6% 1/61 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/109 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Cardiac disorders ATRIAL FIBRILLATION	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.92% 1/109 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Cardiac disorders MYOCARDIAL INFARCTION	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.92% 1/109 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Eye disorders CATARACT	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	1.6% 1/61 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/109 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
General disorders CHEST PAIN	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	1.6% 1/61 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/109 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Respiratory, thoracic and mediastinal disorders PNEUMOTHORAX	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	1.6% 1/61 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/109 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Cardiac disorders ANGINA PECTORIS	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.85% 1/117 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/109 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.

Other adverse events

Measure	Placebo n=64 participants at risk Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)	Ocrelizumab 400mg n=117 participants at risk Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.	Ocrelizumab 200mg n=131 participants at risk Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.	Ocrelizumab 200mg/ Ocrelizumab 200mg n=61 participants at risk Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 200mg/ Ocrelizumab 400mg n=61 participants at risk Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Ocrelizumab 400mg/ Ocrelizumab 400mg n=109 participants at risk Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 200mg n=29 participants at risk Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2	Placebo/ Ocrelizumab 400mg n=28 participants at risk Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	7.8% 5/64 • Number of events 5 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	10.3% 12/117 • Number of events 12 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	12.2% 16/131 • Number of events 16 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	8.2% 5/61 • Number of events 5 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	23.0% 14/61 • Number of events 14 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	12.8% 14/109 • Number of events 14 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	6.9% 2/29 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	14.3% 4/28 • Number of events 4 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Infections and infestations URINARY TRACT INFECTION	7.8% 5/64 • Number of events 5 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	2.6% 3/117 • Number of events 3 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	5.3% 7/131 • Number of events 7 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	9.8% 6/61 • Number of events 6 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	1.6% 1/61 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	3.7% 4/109 • Number of events 4 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	10.3% 3/29 • Number of events 3 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	7.1% 2/28 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Infections and infestations BRONCHITIS	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	6.6% 4/61 • Number of events 4 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	11.5% 7/61 • Number of events 7 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	6.4% 7/109 • Number of events 7 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	3.4% 1/29 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	10.7% 3/28 • Number of events 3 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Infections and infestations NASOPHARYNGITIS	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	3.3% 2/61 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	3.3% 2/61 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	4.6% 5/109 • Number of events 5 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	6.9% 2/29 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	3.6% 1/28 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Infections and infestations SINUSITIS	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	4.9% 3/61 • Number of events 3 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	3.3% 2/61 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	2.8% 3/109 • Number of events 3 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	6.9% 2/29 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	7.1% 2/28 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
General disorders INFUSION RELATED REACTION	10.9% 7/64 • Number of events 7 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	21.4% 25/117 • Number of events 25 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	21.4% 28/131 • Number of events 28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	31.1% 19/61 • Number of events 19 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	27.9% 17/61 • Number of events 17 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	25.7% 28/109 • Number of events 28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	17.2% 5/29 • Number of events 5 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	21.4% 6/28 • Number of events 6 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
General disorders FATIGUE	6.2% 4/64 • Number of events 4 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	3.4% 4/117 • Number of events 4 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	1.5% 2/131 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	1.6% 1/61 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	3.3% 2/61 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	4.6% 5/109 • Number of events 5 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	3.4% 1/29 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	7.1% 2/28 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Gastrointestinal disorders DIARRHOEA	4.7% 3/64 • Number of events 3 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	3.4% 4/117 • Number of events 4 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	7.6% 10/131 • Number of events 10 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	9.8% 6/61 • Number of events 6 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	3.3% 2/61 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	5.5% 6/109 • Number of events 6 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	3.4% 1/29 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	7.1% 2/28 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Gastrointestinal disorders NAUSEA	6.2% 4/64 • Number of events 4 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	5.1% 6/117 • Number of events 6 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	2.3% 3/131 • Number of events 3 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	4.9% 3/61 • Number of events 3 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	3.3% 2/61 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	6.4% 7/109 • Number of events 7 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	10.3% 3/29 • Number of events 3 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Gastrointestinal disorders VOMITING	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	3.3% 2/61 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	6.6% 4/61 • Number of events 4 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/109 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	3.4% 1/29 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Gastrointestinal disorders GASTROOESOPHAGEAL REFLUX DISEASE	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	1.6% 1/61 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	2.8% 3/109 • Number of events 3 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	10.7% 3/28 • Number of events 3 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Nervous system disorders HEADACHE	6.2% 4/64 • Number of events 4 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	4.3% 5/117 • Number of events 5 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	5.3% 7/131 • Number of events 7 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	8.2% 5/61 • Number of events 5 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	8.2% 5/61 • Number of events 5 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	5.5% 6/109 • Number of events 6 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	6.9% 2/29 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/109 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	7.1% 2/28 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Skin and subcutaneous tissue disorders RASH	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	3.3% 2/61 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.92% 1/109 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	6.9% 2/29 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Respiratory, thoracic and mediastinal disorders OROPHARYNGEAL PAIN	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	1.6% 1/61 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	3.3% 2/61 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	1.8% 2/109 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	7.1% 2/28 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Injury, poisoning and procedural complications JOINT INJURY	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/131 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	1.6% 1/61 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/61 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/109 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	6.9% 2/29 • Number of events 2 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/28 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.
Vascular disorders HYPERTENSION	0.00% 0/64 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/117 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	5.3% 7/131 • Number of events 7 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	6.6% 4/61 • Number of events 4 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	8.2% 5/61 • Number of events 5 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	2.8% 3/109 • Number of events 3 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	0.00% 0/29 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.	3.6% 1/28 • Number of events 1 • From baseline up to 17 months Re-randomized Safety Population: All patients (including those not re-randomized at Week 24) who received any part of the second course and provided at least one assessment of safety prior to Week 48 were included in the Re-randomized Safety Population.

Additional Information

Medical Communications

Hoffmann-La Roche

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