Trial Outcomes & Findings for A Study of Combination Treatment With MabThera (Rituximab) and RoActemra (Tocilizumab) Versus RoActemra in Patients With Rheumatoid Arthritis With an Incomplete Response to Methotrexate (NCT NCT00845832)

Last Updated: 2014-12-24

Results Overview

The Disease Activity Score based on 28 joint count (DAS28) and Erythrocyte Sedimentation Rate (ESR), is a measure of the participant's disease activity. It is based on the Tender Joint Count (TJC \[28 joints\]), Swollen Joint Count (SJC \[28 joints\]), participant's global assessment of disease activity (PtGA) Visual Analog Scale (VAS) in millimeters (mm), and ESR in millimeters per hour (mm/hour). DAS28-ESR scores range from 0 - 10. Definition of LDA was based on DAS28-ESR scores. To achieve LDA the DAS28-ESR had to be (less than or equal to) ≤ 3.2. DAS28-ESR equals (=) (0.56 times (\*) (square root)√ TJC plus (+) (0.28 \* √ SJC + (0.70 \* ln(ESR))+(0.014 \* (Global Health) GH) Where: TJC = based on 28 joints SJC = based on 28 joints ESR = erythrocyte sedimentation rate in mm/hour GH = participant's global assessment of disease activity ln = natural log

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

24 participants

Primary outcome timeframe

Week 16

Results posted on

2014-12-24

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo + Tocilizumab (TCZ) 8 Milligrams Per Kilogram (mg/kg) Participants received placebo intravenously (iv) on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.	Rituximab (0.5 Grams [g]) + TCZ (2 mg/kg) Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.	Rituximab (0.5 g) + TCZ (4 mg/kg) Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.
Treatment Period STARTED	4	10	10
Treatment Period COMPLETED	3	7	10
Treatment Period NOT COMPLETED	1	3	0
Safety Follow-Up STARTED	3	9	12
Safety Follow-Up COMPLETED	2	9	12
Safety Follow-Up NOT COMPLETED	1	0	0
Extended Safety Follow-Up STARTED	2	5	7
Extended Safety Follow-Up COMPLETED	2	5	0
Extended Safety Follow-Up NOT COMPLETED	0	0	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo + Tocilizumab (TCZ) 8 Milligrams Per Kilogram (mg/kg) Participants received placebo intravenously (iv) on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.	Rituximab (0.5 Grams [g]) + TCZ (2 mg/kg) Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.	Rituximab (0.5 g) + TCZ (4 mg/kg) Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.
Treatment Period Adverse Event	0	2	0
Treatment Period Protocol Violation	1	1	0
Safety Follow-Up Withdrawal by Subject	1	0	0
Extended Safety Follow-Up Withdrawal by Subject	0	0	7

Baseline Characteristics

A Study of Combination Treatment With MabThera (Rituximab) and RoActemra (Tocilizumab) Versus RoActemra in Patients With Rheumatoid Arthritis With an Incomplete Response to Methotrexate

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo + TCZ (8 mg/kg) n=3 Participants Participants received placebo iv on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.	Rituximab (0.5 g) + TCZ (2 mg/kg) n=9 Participants Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.	Rituximab (0.5 g) + TCZ (4 mg/kg) n=12 Participants Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.	Total n=24 Participants Total of all reporting groups
Age, Continuous	41.3 years STANDARD_DEVIATION 11.02 • n=5 Participants	48.2 years STANDARD_DEVIATION 10.50 • n=7 Participants	50.0 years STANDARD_DEVIATION 6.97 • n=5 Participants	48.3 years STANDARD_DEVIATION 8.94 • n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants	20 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants

PRIMARY outcome

Timeframe: Week 16

Population: Intent-to-Treat (ITT) Population: all randomized participants who received any part of an infusion of study medication. Last observation carried forward (LOCF) used for TJC and SJC, ESR and PtGA. If DAS28-ESR value was missing LDA was missing.

Outcome measures

Outcome measures
Measure	Placebo + TCZ (8 mg/kg) n=4 Participants Participants received placebo iv on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.	Rituximab (0.5 g) + TCZ (2 mg/kg) n=9 Participants Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.	Rituximab (0.5 g) + TCZ (4 mg/kg) n=10 Participants Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.
Percentage of Participants Achieving Low Disease Activity (LDA) at Week 16 Assessed Using Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR)	50.0 percentage of participants	11.1 percentage of participants	20.0 percentage of participants

SECONDARY outcome

Timeframe: Week 16

Population: ITT Population; LOCF used for TJC, ESR, and PtGA. If the DAS28-ESR value was missing then remission or LDA was missing.

Outcome measures

Outcome measures
Measure	Placebo + TCZ (8 mg/kg) n=4 Participants Participants received placebo iv on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.	Rituximab (0.5 g) + TCZ (2 mg/kg) n=9 Participants Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.	Rituximab (0.5 g) + TCZ (4 mg/kg) n=10 Participants Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.
Percentage of Participants Achieving Remission at Week 16 Assessed Using DAS28-ESR	0.0 percentage of participants	0.0 percentage of participants	10.0 percentage of participants

SECONDARY outcome

Timeframe: Week 16

Population: ITT Population; No imputation used for TJC, SJC, ESR, and PtGA. EULAR response was set to missing when the DAS28 score was missing.

DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline (greater than) \>1.2 with DAS28 ≤3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to ≤5.1 or DAS28-ESR \>5.1 or change from baseline \>0.6 to ≤1.2 with DAS28 ≤5.1; nonresponders: change from baseline ≤0.6 or change from baseline \>0.6 and ≤1.2 with DAS28 \>5.1.

Outcome measures

Outcome measures
Measure	Placebo + TCZ (8 mg/kg) n=4 Participants Participants received placebo iv on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.	Rituximab (0.5 g) + TCZ (2 mg/kg) n=9 Participants Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.	Rituximab (0.5 g) + TCZ (4 mg/kg) n=9 Participants Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.
Percentage of Participants by European League Against Rheumatism (EULAR) Response Category at Week 16 No Response	0.0 percentage of participants	22.2 percentage of participants	11.1 percentage of participants
Percentage of Participants by European League Against Rheumatism (EULAR) Response Category at Week 16 Moderate Response	50.0 percentage of participants	66.7 percentage of participants	66.7 percentage of participants
Percentage of Participants by European League Against Rheumatism (EULAR) Response Category at Week 16 Good Response	50.0 percentage of participants	11.1 percentage of participants	22.2 percentage of participants

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48

Population: ITT Population; number (n) = number of participants analyzed at the specified visit.

The DAS28-ESR score is a measure of the participant's disease activity. It is based on the TJC (28 joints), SJC (28 joints), participant's global assessment of disease activity (mm), and ESR (mm/hour). DAS28-ESR is expressed as a score on a scale with the minimum score=0 (best) to maximum score=10 (worst). DAS28-ESR scores were calculated as follows: DAS28-ESR = (0.56 \* √TJC)+(0.28 \* √SJC)+(0.70 \* ln(ESR))+(0.014 \* GH). No imputation used for tender and swollen joint counts, ESR, and patient's global assessment of disease activity VAS.

Outcome measures

Outcome measures
Measure	Placebo + TCZ (8 mg/kg) n=4 Participants Participants received placebo iv on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.	Rituximab (0.5 g) + TCZ (2 mg/kg) n=10 Participants Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.	Rituximab (0.5 g) + TCZ (4 mg/kg) n=10 Participants Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.
Change From Baseline in DAS28-ESR Week 4 (n=4,9,10)	-1.9 units on a scale Standard Deviation 1.73	-0.7 units on a scale Standard Deviation 1.44	-1.0 units on a scale Standard Deviation 0.72
Change From Baseline in DAS28-ESR Week 8 (n=4,10,10)	-2.7 units on a scale Standard Deviation 0.55	-0.5 units on a scale Standard Deviation 1.33	-1.9 units on a scale Standard Deviation 1.31
Change From Baseline in DAS28-ESR Week 12 (n=4,10,9)	-2.7 units on a scale Standard Deviation 0.57	-1.2 units on a scale Standard Deviation 1.60	-2.3 units on a scale Standard Deviation 1.36
Change From Baseline in DAS28-ESR Week 16 (n=4,9,9)	-3.0 units on a scale Standard Deviation 0.80	-1.8 units on a scale Standard Deviation 1.44	-2.3 units on a scale Standard Deviation 1.25
Change From Baseline in DAS28-ESR Week 20 (n=4,9,9)	-3.6 units on a scale Standard Deviation 0.70	-2.2 units on a scale Standard Deviation 1.16	-2.7 units on a scale Standard Deviation 1.45
Change From Baseline in DAS28-ESR Week 24 (n=4,9,8)	-3.5 units on a scale Standard Deviation 1.28	-2.2 units on a scale Standard Deviation 1.14	-2.9 units on a scale Standard Deviation 1.34
Change From Baseline in DAS28-ESR Week 32 (n=4,9,8)	-2.6 units on a scale Standard Deviation 1.62	-3.1 units on a scale Standard Deviation 1.92	-3.3 units on a scale Standard Deviation 1.83
Change From Baseline in DAS28-ESR Week 40 (n=3,8,8)	-2.6 units on a scale Standard Deviation 1.24	-2.2 units on a scale Standard Deviation 1.63	-2.7 units on a scale Standard Deviation 1.02
Change From Baseline in DAS28-ESR Week 48 (n=4,8,7)	-3.3 units on a scale Standard Deviation 1.84	-2.9 units on a scale Standard Deviation 1.50	-3.0 units on a scale Standard Deviation 1.24

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48

Population: ITT Population; n=number of participants analyzed for the given parameter at the specified timepoint.

The Clinical Disease Activity Index (CDAI) score was calculated according to the following formula: CDAI = SJC + TJC + GH/10 + EGA/10 Where: SJC = swollen joint count based on 28 joints; TJC = tender joint count based on 28 joints; GH = Participant's global assessment of disease activity; EGA = evaluator's (physician's) global assessment of disease activity. CDAI scores range from 0-76 and the following cut-off points for different disease activity states have been used: high disease activity \>22; moderate disease activity \>10 and ≤22; LDA \>2.8 and ≤10; and remission ≤ 2.8. No imputation used for TJC, SJC, Patient's Global Assessment of Disease Activity VAS and Physicians global assessment of disease activity VAS.

Outcome measures

Outcome measures
Measure	Placebo + TCZ (8 mg/kg) n=4 Participants Participants received placebo iv on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.	Rituximab (0.5 g) + TCZ (2 mg/kg) n=10 Participants Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.	Rituximab (0.5 g) + TCZ (4 mg/kg) n=10 Participants Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.
Clinical Disease Activity Index Scores Week 4 (n=4, 8, 10)	21.2 units on a scale Standard Deviation 14.19	23.4 units on a scale Standard Deviation 12.38	20.0 units on a scale Standard Deviation 6.97
Clinical Disease Activity Index Scores Week 8 (n=4,10,10)	14.6 units on a scale Standard Deviation 4.38	29.4 units on a scale Standard Deviation 14.91	15.5 units on a scale Standard Deviation 9.96
Clinical Disease Activity Index Scores Week 12 (n=4,10, 9)	16.3 units on a scale Standard Deviation 10.52	23.2 units on a scale Standard Deviation 12.47	13.4 units on a scale Standard Deviation 8.40
Clinical Disease Activity Index Scores Week 16 (n=4,10, 9)	9.5 units on a scale Standard Deviation 5.70	19.5 units on a scale Standard Deviation 15.42	12.7 units on a scale Standard Deviation 8.32
Clinical Disease Activity Index Scores Week 20 (n=4, 8, 9)	10.8 units on a scale Standard Deviation 4.46	15.4 units on a scale Standard Deviation 7.76	11.6 units on a scale Standard Deviation 6.64
Clinical Disease Activity Index Scores Week 24 (n=4, 9, 8)	9.2 units on a scale Standard Deviation 6.71	12.6 units on a scale Standard Deviation 3.98	10.9 units on a scale Standard Deviation 5.47
Clinical Disease Activity Index Scores Week 32 (n=4, 9, 8)	15.2 units on a scale Standard Deviation 10.42	11.5 units on a scale Standard Deviation 13.14	9.3 units on a scale Standard Deviation 9.42
Clinical Disease Activity Index Scores Week 40 (n=3, 8, 8)	20.3 units on a scale Standard Deviation 8.35	17.9 units on a scale Standard Deviation 16.40	11.8 units on a scale Standard Deviation 5.31
Clinical Disease Activity Index Scores Week 48 (n=4, 7, 8)	11.6 units on a scale Standard Deviation 10.11	12.8 units on a scale Standard Deviation 12.15	7.1 units on a scale Standard Deviation 6.41
Clinical Disease Activity Index Scores Baseline (n=4, 10, 10)	37.7 units on a scale Standard Deviation 4.59	36.4 units on a scale Standard Deviation 9.16	33.0 units on a scale Standard Deviation 7.69

Adverse Events

Placebo + TCZ (8 mg/kg)

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Rituximab (0.5 g) + TCZ (2 mg/kg)

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Rituximab (0.5 g) + TCZ (4 mg/kg)

Serious events: 3 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo + TCZ (8 mg/kg) n=3 participants at risk Participants received placebo iv on Days 1 and 15 followed by TCZ 8 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.	Rituximab (0.5 g) + TCZ (2 mg/kg) n=9 participants at risk Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 2 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.	Rituximab (0.5 g) + TCZ (4 mg/kg) n=12 participants at risk Participants received rituximab 0.5 g iv on Days 1 and 15 followed by TCZ 4 mg/kg iv at Weeks 4, 8, 12 and 16. Participants also continued to receive a stable dose of methotrexate, between 7.5 and 25 mg/week orally or parenterally, as prescribed by the physician and in accordance with the local label. Participants also received a stable dose of folic acid.
General disorders Chest pain	0.00% 0/3 • Adverse Events were recorded throughout the study from the date of first study drug administration until 48 weeks of treatment period and for those in the Safety follow up population until the end of follow up period. Participants who received the incorrect therapy from that intended were summarized in the group according to the therapy actually received for the majority of the time through Week 48. 1 participant each from Placebo + TCZ (8 mg/kg) and Rituximab (0.5 g) + TCZ (2 mg/kg) groups was included in Rituximab (0.5 g) + TCZ (4 mg/kg) group.	0.00% 0/9 • Adverse Events were recorded throughout the study from the date of first study drug administration until 48 weeks of treatment period and for those in the Safety follow up population until the end of follow up period. Participants who received the incorrect therapy from that intended were summarized in the group according to the therapy actually received for the majority of the time through Week 48. 1 participant each from Placebo + TCZ (8 mg/kg) and Rituximab (0.5 g) + TCZ (2 mg/kg) groups was included in Rituximab (0.5 g) + TCZ (4 mg/kg) group.	8.3% 1/12 • Adverse Events were recorded throughout the study from the date of first study drug administration until 48 weeks of treatment period and for those in the Safety follow up population until the end of follow up period. Participants who received the incorrect therapy from that intended were summarized in the group according to the therapy actually received for the majority of the time through Week 48. 1 participant each from Placebo + TCZ (8 mg/kg) and Rituximab (0.5 g) + TCZ (2 mg/kg) groups was included in Rituximab (0.5 g) + TCZ (4 mg/kg) group.
General disorders Infusion related reaction	0.00% 0/3 • Adverse Events were recorded throughout the study from the date of first study drug administration until 48 weeks of treatment period and for those in the Safety follow up population until the end of follow up period. Participants who received the incorrect therapy from that intended were summarized in the group according to the therapy actually received for the majority of the time through Week 48. 1 participant each from Placebo + TCZ (8 mg/kg) and Rituximab (0.5 g) + TCZ (2 mg/kg) groups was included in Rituximab (0.5 g) + TCZ (4 mg/kg) group.	11.1% 1/9 • Adverse Events were recorded throughout the study from the date of first study drug administration until 48 weeks of treatment period and for those in the Safety follow up population until the end of follow up period. Participants who received the incorrect therapy from that intended were summarized in the group according to the therapy actually received for the majority of the time through Week 48. 1 participant each from Placebo + TCZ (8 mg/kg) and Rituximab (0.5 g) + TCZ (2 mg/kg) groups was included in Rituximab (0.5 g) + TCZ (4 mg/kg) group.	0.00% 0/12 • Adverse Events were recorded throughout the study from the date of first study drug administration until 48 weeks of treatment period and for those in the Safety follow up population until the end of follow up period. Participants who received the incorrect therapy from that intended were summarized in the group according to the therapy actually received for the majority of the time through Week 48. 1 participant each from Placebo + TCZ (8 mg/kg) and Rituximab (0.5 g) + TCZ (2 mg/kg) groups was included in Rituximab (0.5 g) + TCZ (4 mg/kg) group.
Gastrointestinal disorders Large intestinal ulcer haemorrhage	0.00% 0/3 • Adverse Events were recorded throughout the study from the date of first study drug administration until 48 weeks of treatment period and for those in the Safety follow up population until the end of follow up period. Participants who received the incorrect therapy from that intended were summarized in the group according to the therapy actually received for the majority of the time through Week 48. 1 participant each from Placebo + TCZ (8 mg/kg) and Rituximab (0.5 g) + TCZ (2 mg/kg) groups was included in Rituximab (0.5 g) + TCZ (4 mg/kg) group.	0.00% 0/9 • Adverse Events were recorded throughout the study from the date of first study drug administration until 48 weeks of treatment period and for those in the Safety follow up population until the end of follow up period. Participants who received the incorrect therapy from that intended were summarized in the group according to the therapy actually received for the majority of the time through Week 48. 1 participant each from Placebo + TCZ (8 mg/kg) and Rituximab (0.5 g) + TCZ (2 mg/kg) groups was included in Rituximab (0.5 g) + TCZ (4 mg/kg) group.	8.3% 1/12 • Adverse Events were recorded throughout the study from the date of first study drug administration until 48 weeks of treatment period and for those in the Safety follow up population until the end of follow up period. Participants who received the incorrect therapy from that intended were summarized in the group according to the therapy actually received for the majority of the time through Week 48. 1 participant each from Placebo + TCZ (8 mg/kg) and Rituximab (0.5 g) + TCZ (2 mg/kg) groups was included in Rituximab (0.5 g) + TCZ (4 mg/kg) group.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	33.3% 1/3 • Adverse Events were recorded throughout the study from the date of first study drug administration until 48 weeks of treatment period and for those in the Safety follow up population until the end of follow up period. Participants who received the incorrect therapy from that intended were summarized in the group according to the therapy actually received for the majority of the time through Week 48. 1 participant each from Placebo + TCZ (8 mg/kg) and Rituximab (0.5 g) + TCZ (2 mg/kg) groups was included in Rituximab (0.5 g) + TCZ (4 mg/kg) group.	0.00% 0/9 • Adverse Events were recorded throughout the study from the date of first study drug administration until 48 weeks of treatment period and for those in the Safety follow up population until the end of follow up period. Participants who received the incorrect therapy from that intended were summarized in the group according to the therapy actually received for the majority of the time through Week 48. 1 participant each from Placebo + TCZ (8 mg/kg) and Rituximab (0.5 g) + TCZ (2 mg/kg) groups was included in Rituximab (0.5 g) + TCZ (4 mg/kg) group.	0.00% 0/12 • Adverse Events were recorded throughout the study from the date of first study drug administration until 48 weeks of treatment period and for those in the Safety follow up population until the end of follow up period. Participants who received the incorrect therapy from that intended were summarized in the group according to the therapy actually received for the majority of the time through Week 48. 1 participant each from Placebo + TCZ (8 mg/kg) and Rituximab (0.5 g) + TCZ (2 mg/kg) groups was included in Rituximab (0.5 g) + TCZ (4 mg/kg) group.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/3 • Adverse Events were recorded throughout the study from the date of first study drug administration until 48 weeks of treatment period and for those in the Safety follow up population until the end of follow up period. Participants who received the incorrect therapy from that intended were summarized in the group according to the therapy actually received for the majority of the time through Week 48. 1 participant each from Placebo + TCZ (8 mg/kg) and Rituximab (0.5 g) + TCZ (2 mg/kg) groups was included in Rituximab (0.5 g) + TCZ (4 mg/kg) group.	11.1% 1/9 • Adverse Events were recorded throughout the study from the date of first study drug administration until 48 weeks of treatment period and for those in the Safety follow up population until the end of follow up period. Participants who received the incorrect therapy from that intended were summarized in the group according to the therapy actually received for the majority of the time through Week 48. 1 participant each from Placebo + TCZ (8 mg/kg) and Rituximab (0.5 g) + TCZ (2 mg/kg) groups was included in Rituximab (0.5 g) + TCZ (4 mg/kg) group.	0.00% 0/12 • Adverse Events were recorded throughout the study from the date of first study drug administration until 48 weeks of treatment period and for those in the Safety follow up population until the end of follow up period. Participants who received the incorrect therapy from that intended were summarized in the group according to the therapy actually received for the majority of the time through Week 48. 1 participant each from Placebo + TCZ (8 mg/kg) and Rituximab (0.5 g) + TCZ (2 mg/kg) groups was included in Rituximab (0.5 g) + TCZ (4 mg/kg) group.
Infections and infestations Pneumonia	0.00% 0/3 • Adverse Events were recorded throughout the study from the date of first study drug administration until 48 weeks of treatment period and for those in the Safety follow up population until the end of follow up period. Participants who received the incorrect therapy from that intended were summarized in the group according to the therapy actually received for the majority of the time through Week 48. 1 participant each from Placebo + TCZ (8 mg/kg) and Rituximab (0.5 g) + TCZ (2 mg/kg) groups was included in Rituximab (0.5 g) + TCZ (4 mg/kg) group.	11.1% 1/9 • Adverse Events were recorded throughout the study from the date of first study drug administration until 48 weeks of treatment period and for those in the Safety follow up population until the end of follow up period. Participants who received the incorrect therapy from that intended were summarized in the group according to the therapy actually received for the majority of the time through Week 48. 1 participant each from Placebo + TCZ (8 mg/kg) and Rituximab (0.5 g) + TCZ (2 mg/kg) groups was included in Rituximab (0.5 g) + TCZ (4 mg/kg) group.	0.00% 0/12 • Adverse Events were recorded throughout the study from the date of first study drug administration until 48 weeks of treatment period and for those in the Safety follow up population until the end of follow up period. Participants who received the incorrect therapy from that intended were summarized in the group according to the therapy actually received for the majority of the time through Week 48. 1 participant each from Placebo + TCZ (8 mg/kg) and Rituximab (0.5 g) + TCZ (2 mg/kg) groups was included in Rituximab (0.5 g) + TCZ (4 mg/kg) group.
Gastrointestinal disorders Umbilical hernia	0.00% 0/3 • Adverse Events were recorded throughout the study from the date of first study drug administration until 48 weeks of treatment period and for those in the Safety follow up population until the end of follow up period. Participants who received the incorrect therapy from that intended were summarized in the group according to the therapy actually received for the majority of the time through Week 48. 1 participant each from Placebo + TCZ (8 mg/kg) and Rituximab (0.5 g) + TCZ (2 mg/kg) groups was included in Rituximab (0.5 g) + TCZ (4 mg/kg) group.	0.00% 0/9 • Adverse Events were recorded throughout the study from the date of first study drug administration until 48 weeks of treatment period and for those in the Safety follow up population until the end of follow up period. Participants who received the incorrect therapy from that intended were summarized in the group according to the therapy actually received for the majority of the time through Week 48. 1 participant each from Placebo + TCZ (8 mg/kg) and Rituximab (0.5 g) + TCZ (2 mg/kg) groups was included in Rituximab (0.5 g) + TCZ (4 mg/kg) group.	8.3% 1/12 • Adverse Events were recorded throughout the study from the date of first study drug administration until 48 weeks of treatment period and for those in the Safety follow up population until the end of follow up period. Participants who received the incorrect therapy from that intended were summarized in the group according to the therapy actually received for the majority of the time through Week 48. 1 participant each from Placebo + TCZ (8 mg/kg) and Rituximab (0.5 g) + TCZ (2 mg/kg) groups was included in Rituximab (0.5 g) + TCZ (4 mg/kg) group.

Other adverse events

Additional Information

Medical Communications

Hoffmann- LaRoche

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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 after the first publication or presentation that involves the overall study. Sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
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Restriction type: OTHER