Trial Outcomes & Findings for A Study to Evaluate Rituximab in Combination With Methotrexate in Methotrexate-Naive Patients With Active Rheumatoid Arthritis (NCT NCT00299104)

Last Updated: 2017-07-28

Results Overview

Rate of progression in structural joint damage (PJD) by change in Total Modified Sharp Score (TMSS) from screening to Week 52 in the modified intent-to-treat (MITT) population. TMSS is the sum of the erosion score (ES) and the joint space narrowing (JSN) score and has a range of 0 to 398. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change and higher scores represent a worsening of joint erosions and joint space narrowing.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

755 participants

Primary outcome timeframe

Baseline and week 52

Results posted on

2017-07-28

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo + Methotrexate Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Treatment Period STARTED	251	252	252
Treatment Period Safety/ITT: Received Study Drug	249	249	250
Treatment Period Completed Week 24	227	240	241
Treatment Period Completed Week 52	213	227	232
Treatment Period Completed Week 104	178	213	216
Treatment Period COMPLETED	62	77	80
Treatment Period NOT COMPLETED	189	175	172
Safety Follow-Up (SFU) Period STARTED	184	212	213
Safety Follow-Up (SFU) Period COMPLETED	129	171	176
Safety Follow-Up (SFU) Period NOT COMPLETED	55	41	37
Extended Safety Follow-Up (ESFU) Period STARTED	34	40	51
Extended Safety Follow-Up (ESFU) Period COMPLETED	29	31	39
Extended Safety Follow-Up (ESFU) Period NOT COMPLETED	5	9	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo + Methotrexate Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Treatment Period Adverse Event	14	9	7
Treatment Period Death	1	1	1
Treatment Period Insufficient therapeutic response	34	13	8
Treatment Period Failure to return	9	8	8
Treatment Period Violation of selection criteria	1	2	0
Treatment Period Protocol Violation	1	1	0
Treatment Period Refused treatment	9	2	2
Treatment Period Withdrew consent	14	19	9
Treatment Period Administrative reasons	106	120	137
Safety Follow-Up (SFU) Period Death	3	2	1
Safety Follow-Up (SFU) Period Lost to Follow-up	9	11	20
Safety Follow-Up (SFU) Period Withdrawal by Subject	16	21	11
Safety Follow-Up (SFU) Period Administrative reasons	27	7	5
Extended Safety Follow-Up (ESFU) Period Death	0	1	0
Extended Safety Follow-Up (ESFU) Period Lost to Follow-up	2	2	2
Extended Safety Follow-Up (ESFU) Period Withdrawal by Subject	2	4	8
Extended Safety Follow-Up (ESFU) Period Administrative reasons	1	2	2

Baseline Characteristics

A Study to Evaluate Rituximab in Combination With Methotrexate in Methotrexate-Naive Patients With Active Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo + Methotrexate n=249 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=249 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=250 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Total n=748 Participants Total of all reporting groups
Age, Continuous	48.06 years STANDARD_DEVIATION 12.692 • n=5 Participants	47.87 years STANDARD_DEVIATION 13.391 • n=7 Participants	47.89 years STANDARD_DEVIATION 13.324 • n=5 Participants	47.94 years STANDARD_DEVIATION 13.136 • n=4 Participants
Sex: Female, Male Female	192 Participants n=5 Participants	203 Participants n=7 Participants	212 Participants n=5 Participants	607 Participants n=4 Participants
Sex: Female, Male Male	57 Participants n=5 Participants	46 Participants n=7 Participants	38 Participants n=5 Participants	141 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and week 52

Population: Modified intent-to-treat population includes patients with a screening and at least one post-baseline radiographic evaluation, grouped as randomized. Linear interpolation/extrapolation used for missing data.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=232 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=239 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=244 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Change From Baseline in Modified Total Sharp Score (mTSS) From Screening at Week 52	1.079 Score on a scale Standard Deviation 4.0934	0.646 Score on a scale Standard Deviation 1.9196	0.359 Score on a scale Standard Deviation 1.0095

SECONDARY outcome

Timeframe: Baseline and week 52

Rate of progression in structural joint damage (PJD) by change in modified Sharp erosion score from screening to Week 52. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. A score of 0 would indicate no change and higher scores represent a worsening of joint erosions.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=232 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=239 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=244 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Change From Baseline in Modified Sharp Erosion Score at Week 52	0.738 Score on a scale Standard Deviation 2.0480	0.453 Score on a scale Standard Deviation 1.2065	0.233 Score on a scale Standard Deviation 0.6252

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Modified intent-to-treat population includes patients with a screening and at least one post-baseline radiographic evaluation, grouped as randomized. Patients with missing data are classified as progressing.

Percentage of patients without radiographic progression at Week 52, defined as change in total modified Sharp score (TMSS) \<= 0. TMSS is the sum of the erosion score (ES) and the joint space narrowing (JSN) score and has a range of 0 to 398. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=232 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=239 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=244 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Percentage of Patients Without Radiographic Progression at Week 52	53.4 Percentage	57.7 Percentage	63.5 Percentage

SECONDARY outcome

Timeframe: Baseline, Week 52

No radiographic progression is defined as a change in the total erosion score at Week 52 of less than or equal to zero.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=232 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=239 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=244 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Percentage of Patients Without Radiographic Progression in Total Erosion Score at Week 52	54.7 Percentage of Participants	59.0 Percentage of Participants	66.8 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline and week 52

Rate of progression in structural joint damage (PJD) by change in modified joint space narrowing (JSN) from screening to Week 52. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change and higher scores represent a worsening of joint space narrowing.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=232 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=239 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=244 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Change From Baseline in Modified Joint Space Narrowing (JSN) Score at Week 52	0.341 Score on a scale Standard Deviation 2.2408	0.193 Score on a scale Standard Deviation 0.9422	0.126 Score on a scale Standard Deviation 0.6363

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the Modified Intent to Treat (MITT) population includes all randomized participants who received at least one infusion and had both screening and post-baseline radiographic assessments at the given time point for analysis.

The modified total sharp score is the sum of the erosion score (ES) and the joint space narrowing (JSN) score and has a range of 0 to 398. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change and higher scores represent a worsening of joint erosions and joint space narrowing.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=226 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=238 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=242 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Change From Baseline in the Modified Total Sharp Score at Week 24	0.701 Score on a scale Standard Deviation 2.9116	0.508 Score on a scale Standard Deviation 1.7349	0.328 Score on a scale Standard Deviation 0.9443

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Participants from the modified intent-to-treat population (includes patients with a screening and at least one post-baseline radiographic evaluation, grouped as randomized) who had data available at Week 24 for analysis.

Total Erosion Score is determined by evaluation of fourteen sites in each wrist and hand and six joints in each foot using an eight-point scale from 0 (normal: no erosions) to 3.5 (Very severe; erosions of 100% of the articular surfaces. The Total Erosion Score at Week 24 - Total Erosion Score at baseline is calculated.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=226 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=238 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=242 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Change From Baseline in the Total Erosion Score at Week 24	0.491 Score on a scale Standard Deviation 1.3789	0.404 Score on a scale Standard Deviation 1.0390	0.220 Score on a scale Standard Deviation 0.5802

SECONDARY outcome

Timeframe: Baseline, Week 24

Joint Space Narrowing is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change and higher scores represent a worsening of joint space narrowing.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=226 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=238 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=242 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Change From Baseline in Modified Joint Space Narrowing (JSN) Score at Week 24	0.210 Score on a scale Standard Deviation 1.7403	0.176 Score on a scale Standard Deviation 0.8949	0.108 Score on a scale Standard Deviation 0.6118

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Modified Intent to Treat (MITT) population includes all randomized participants who received at least one infusion and had both screening and post-baseline radiographic assessments. Patients with missing data are classified as progressing

Percentage of patients without radiographic progression at Week 24 defined as change in total modified Sharp score (TMSS) ≤ 0. TMSS is the sum of the erosion score (ES) and the joint space narrowing (JSN) score and has a range of 0 to 398. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=233 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=239 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=244 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Percentage of Participants Without Radiographic Progression at Week 24	59.7 Percentage of Participants	65.3 Percentage of Participants	71.7 Percentage of Participants

SECONDARY outcome

Timeframe: Week 52

Population: Intent to treat (ITT) population includes all randomized participants who received at least one infusion. Patients are considered non-responders if data are missing or from the point of withdrawal, rescue use or receipt of non-permitted Disease-modifying anti-rheumatic drugs (DMARDs).

To achieve an ACR50 response requires at least a 50% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 50% improvement in three of five additional measurements from: * the physician's global assessment of disease activity * patient's global assessment of disease activity * patient's assessment of pain * HAQ-DI (Health Assessment Questionnaire disability index) * an acute phase reactant C-Reactive Protein (CRP). (If CRP was missing then Erythrocyte Sedimentation Rate (ESR) was used if available.)

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=249 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=249 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=250 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Percentage of Participants With American College of Rheumatology (ACR) ACR50 Response at Week 52	41.8 Percentage of Participants	59.4 Percentage of Participants	64.8 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants from the Intent to treat (ITT) population includes all randomized participants who received at least one infusion who had data available for analyses. Last observation carried forward.

DAS28-ESR is calculated from the following formula: (0.56 \* TJC) + (0.28 \* SJC) + (0.70 \* ln ESR) + (0.014 \* GH) TJC = tender joint count, based on 28 joints SJC = swollen joint count, based on 28 joints ESR = erythrocyte sedimentation rate in mm/h GH = patient's global assessment of disease activity A DAS28-ESR score of 5.1 or above is considered to indicate high disease activity. Patients can also be defined as having low disease activity (DAS28-ESR ≤ 3.2) or remission (DAS28-ESR \< 2.6).

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=244 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=247 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=248 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Change From Baseline in the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 52	-2.33 Score on a scale Standard Deviation 1.691	-3.35 Score on a scale Standard Deviation 1.663	-3.46 Score on a scale Standard Deviation 1.640

SECONDARY outcome

Timeframe: Baseline, Week 52

To achieve an ACR70 response requires at least a 70% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 70% improvement in three of five additional measurements from: * the physician's global assessment of disease activity * patient's global assessment of disease activity * patient's assessment of pain * HAQ-DI (Health Assessment Questionnaire disability index) * an acute phase reactant C-Reactive Protein (CRP). (If CRP was missing then Erythrocyte Sedimentation Rate (ESR) was used if available.)

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=249 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=249 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=250 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Percentage of Participants With American College of Rheumatology (ACR) ACR70 Response at Week 52	24.9 Percentage of Participants	42.2 Percentage of Participants	46.8 Percentage of Participants

SECONDARY outcome

Timeframe: Week 52

Population: Participants from the Intent to treat (ITT) population includes all randomized participants who received at least one infusion with data available for analyses.

The DAS28-4(ESR) score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm), and ESR. DAS28-4(ESR) scores range from 0 - 10. Remission is defined as achieving a DAS28-ESR score of less than 2.6

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=247 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=248 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=249 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Percentage of Participants With DAS28-ESR Remission at Week 52	12.6 Percentage of Participants	25.4 Percentage of Participants	30.5 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Intent to treat (ITT) population includes all randomized participants who received at least one infusion. Patients are considered non-responders if data are missing

European League Against Rheumatism (EULAR) criteria reflects an improvement in disease activity and an attainment of a lower degree of disease activity. A good response is defined as an improvement in the DAS28-ESR of \> 1.2 compared with baseline, and attainment of a DAS28-ESR of \< 3.2.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=249 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=249 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=250 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Percentage of Participants With European League Against Rheumatism (EULAR) Good Response at Week 52	18.1 Percentage of Participants	39.0 Percentage of Participants	41.6 Percentage of Participants

SECONDARY outcome

Timeframe: Week 52

Population: Intent to treat (ITT) population includes all randomized participants who received at least one infusion.

Major clinical response is defined as a continuous six-month period of success by the ACR70. ACR70= 70% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 70% improvement in 3 of five additional measurements from: * the physician's global assessment of disease activity * patient's global assessment of disease activity * patient's assessment of pain * HAQ-DI (Health Assessment Questionnaire disability index) * an acute phase reactant C-Reactive Protein (CRP). (If CRP was missing then Erythrocyte Sedimentation Rate (ESR) was used if available.)

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=249 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=249 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=250 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
The Percentage of Participants With Major Clinical Response at Week 52	8.4 Percentage of Participants	18.1 Percentage of Participants	21.2 Percentage of Participants

SECONDARY outcome

Timeframe: Week 52

Population: Participants from the Intent to treat (ITT) population includes all randomized participants who received at least one infusion who had data available for analyses.

The DAS28-4(ESR) score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm), and ESR. DAS28-4(ESR) scores range from 0 - 10. Low disease activity is defined as achieving a DAS28-ESR score of less than or equal to 3.2

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=247 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=248 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=249 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Percentage of Participants With DAS28-ESR Low Disease Activity at Week 52	19.8 Percentage of Participants	40.3 Percentage of Participants	43.0 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, Week 52

To achieve an ACR20 response requires at least a 20% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 20% improvement in three of five additional measurements from: * the physician's global assessment of disease activity * patient's global assessment of disease activity * patient's assessment of pain * HAQ-DI (Health Assessment Questionnaire disability index) * an acute phase reactant C-Reactive Protein (CRP). (If CRP was missing then Erythrocyte Sedimentation Rate (ESR) was used if available.)

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=249 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=249 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=250 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Percentage of Participants With American College of Rheumatology (ACR) ACR20 Response at Week 52	64.3 Percentage of Participants	76.7 Percentage of Participants	80.0 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, Week 52

To achieve an ACR90 response requires at least a 90% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 90% improvement in three of five additional measurements from: * the physician's global assessment of disease activity * patient's global assessment of disease activity * patient's assessment of pain * HAQ-DI (Health Assessment Questionnaire disability index) * an acute phase reactant C-Reactive Protein (CRP). (If CRP was missing then Erythrocyte Sedimentation Rate (ESR) was used if available.)

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=249 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=249 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=250 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Percentage of Participants With American College of Rheumatology (ACR) ACR90 Response at Week 52	9.2 Percentage of Participants	17.3 Percentage of Participants	16.4 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants from the Intent to treat (ITT) population includes all randomized participants who received at least one infusion who had data available for analyses. Observed data.

FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's 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 patient'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). A higher score reflects an improvement in the patient's health status.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=198 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=206 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=218 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Change in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Score From Baseline at Week 52	10.154 Score on a scale Standard Deviation 11.1344	11.833 Score on a scale Standard Deviation 11.5807	12.426 Score on a scale Standard Deviation 12.2535

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Intent-to treat Population includes all randomized participants who received at least one dose of study drug. Last observation carried forward.

The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip,and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0(without any difficulty) to 4 (unable to do).HAQ-DI=sum of worst scores in each domain divided by the number of domains answered. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=248 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=247 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=249 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52	-0.800 Score on a scale Standard Deviation 0.7764	-1.038 Score on a scale Standard Deviation 0.7625	-1.023 Score on a scale Standard Deviation 0.7634

SECONDARY outcome

Timeframe: Baseline, Week 52, Week 104

Population: Intent to treat (ITT) population includes all participants who received at least one infusion. Last observation carried forward. "n" in each of the categories is the number of participants with data available for analyses at the given time point.

The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement. Means are adjusted for baseline value, Rheumatoid Factor status and region.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=249 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=249 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=250 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Change From Baseline in the SF-36 Physical Health Component Summary Score at Week 52 and Week 104 Week 52 (n=239,236,241)	8.953 Score on a scale Standard Deviation 9.3986	11.022 Score on a scale Standard Deviation 9.6246 • Interval -0.331 to 3.504	12.205 Score on a scale Standard Deviation 9.4986 • Interval 1.214 to 5.026
Change From Baseline in the SF-36 Physical Health Component Summary Score at Week 52 and Week 104 Week 104 (n=240,236,242)	8.617 Score on a scale Standard Deviation 9.8500	11.032 Score on a scale Standard Deviation 9.9631 • Interval 1.59 to 4.787	12.649 Score on a scale Standard Deviation 10.4331 • Interval 2.749 to 5.92

SECONDARY outcome

Timeframe: Baseline, Weeks 52, Week 104

Population: Intent to treat (ITT) population includes all randomized participants who received at least one infusion. Last observation carried forward. "n" in each of the categories is the number of participants with data available for analyses at the given time point.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=249 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=249 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=250 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Change From Baseline in the SF-36 Mental Health Component Summary Score at Week 52 and Week 104 Week 52 (n=239,236,241)	6.689 Score on a scale Standard Deviation 13.1160	7.718 Score on a scale Standard Deviation 11.8903	8.167 Score on a scale Standard Deviation 12.1709
Change From Baseline in the SF-36 Mental Health Component Summary Score at Week 52 and Week 104 Week 104 (n= 240,236,242)	6.295 Score on a scale Standard Deviation 13.9813	7.617 Score on a scale Standard Deviation 12.0793	9.066 Score on a scale Standard Deviation 12.5325

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Intent to treat (ITT) population includes all randomized participants who received at least one infusion. Last observation carried forward.

The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. Each domain has at least two component questions. There are four possible responses for each component on a scale of 0 (without difficulty) to 3 (unable to do). Higher scores=greater dysfunction. Improved:HAQ-DI score change \<=-0.22 Unchanged:HAQ-DI score change -0.22 to 0.22 Worsened:HAQ score =\> 0.22

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=249 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=249 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=250 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Percentage of Participants With Categorical Change in Health Assessment Questionnaire- Disability Index (HAQ-DI) From Baseline at Week 52 Improved	77.1 Percentage of participants	86.7 Percentage of participants	86.8 Percentage of participants
Percentage of Participants With Categorical Change in Health Assessment Questionnaire- Disability Index (HAQ-DI) From Baseline at Week 52 Unchanged	14.1 Percentage of participants	8.8 Percentage of participants	8.0 Percentage of participants
Percentage of Participants With Categorical Change in Health Assessment Questionnaire- Disability Index (HAQ-DI) From Baseline at Week 52 Worsened	8.4 Percentage of participants	3.6 Percentage of participants	4.4 Percentage of participants
Percentage of Participants With Categorical Change in Health Assessment Questionnaire- Disability Index (HAQ-DI) From Baseline at Week 52 Not Assessable	0.4 Percentage of participants	0.8 Percentage of participants	0.8 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Participants from the Intent-to-treat population, includes all randomized participants who received at least one dose of study drug, with data available for analysis at Baseline and Week 52. Last observation carried forward.

MCID is defined as a change from baseline in SF-36 Physical Health Component Score of \>5.42. SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=239 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=236 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=242 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Percentage of Patients With Minimally Clinically Important Difference (MCID) in the SF-36 Physical Health Component Score at Week 52	63.2 Percentage of Participants	69.9 Percentage of Participants	76.4 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, Week 52

MCID is defined as a change from baseline in SF-36 Mental Health Component Score of \>6.33. SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=239 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=236 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=242 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Percentage of Patients With Minimally Clinically Important Difference (MCID) in the SF-36 Mental Health Component Score at Week 52	49.0 Percentage of Participants	50.8 Percentage of Participants	57.0 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, Week 104

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=229 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=238 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=243 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Change From Baseline in the Modified Total Sharp Score at Week 104	1.948 Score on a scale Standard Deviation 5.5782	0.761 Score on a scale Standard Deviation 2.6181	0.406 Score on a scale Standard Deviation 1.4312

SECONDARY outcome

Timeframe: Baseline, Week 104

Population: Participants from the Modified Intent to Treat (MITT) population includes all randomized participants who received at least one infusion and who had both screening and post-baseline radiographic assessments at the given time point for analyses. Linear extrapolation used for missing data.

Total Erosion Score is determined by evaluation of fourteen sites in each wrist and hand and six joints in each foot using an eight-point scale from 0 (normal: no erosions) to 3.5 (Very severe; erosions of 100% of the articular surfaces. The change from the score at baseline to week 104 is calculated.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=229 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=238 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=243 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Change From Baseline in the Total Erosion Score at Week 104	1.315 Score on a scale Standard Deviation 3.2466	0.499 Score on a scale Standard Deviation 1.7221	0.227 Score on a scale Standard Deviation 0.7939

SECONDARY outcome

Timeframe: Baseline, Week 104

Percentage of patients without radiographic progression at Week 104, defined as change in total modified Sharp score (TMSS) ≤ 0. TMSS is the sum of the erosion score (ES) and the joint space narrowing (JSN) score and has a range of 0 to 398. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=233 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=239 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=244 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Percentage of Participants Without Radiographic Progression at Week 104	37.3 Percentage of Participants	49.4 Percentage of Participants	56.6 Percentage of Participants

SECONDARY outcome

Timeframe: Week 104

Total Erosion Score is determined by evaluation of fourteen sites in each wrist and hand and six joints in each foot using an eight-point scale from 0 (normal: no erosions) to 3.5 (Very severe; erosions of 100% of the articular surfaces. The score at baseline is compared to the score at week 104. No progression is defined as a change from score at screening to week 104 ≤0.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=233 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=239 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=244 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Percentage of Participants Without Radiographic Progression in the Total Erosion Score at Week 104	38.2 Percentage of Participants	52.7 Percentage of Participants	58.6 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, Week 104

Population: Participants from the Intent-to treat Population includes all randomized participants who received at least one dose of study drug with data at baseline and Week 104 available for analysis. Last observation carried forward.

The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0(without any difficulty) to 4 (unable to do). HAQ-DI=sum of worst scores in each domain divided by the number of domains answered. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo + Methotrexate n=248 Participants Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks.	Rituximab (0.5 g x 2) + Methotrexate n=247 Participants Rituximab intravenously at a dose of 0.5 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6	Rituximab (1.0 g x 2) + Methotrexate n=248 Participants Rituximab intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 104	-0.806 Score on a scale Standard Deviation 0.7968	-1038 Score on a scale Standard Deviation 0.8142	-1.055 Score on a scale Standard Deviation 0.7901

Adverse Events

Placebo + Methotrexate

Serious events: 48 serious events

Other events: 193 other events

Deaths: 0 deaths

Rituximab (0.5 g x 2) + Methotrexate

Serious events: 54 serious events

Other events: 232 other events

Deaths: 0 deaths

Rituximab (1.0 g x 2) + Methotrexate

Serious events: 58 serious events

Other events: 208 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Genentech, Inc.

Phone: 800-821-8590

Email: [email protected]

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