Trial Outcomes & Findings for A Study of Ocrelizumab Compared to Placebo in Patients With Active Rheumatoid Arthritis Continuing Methotrexate Treatment (STAGE) (NCT NCT00406419)

Last Updated: 2020-11-27

Results Overview

ACR20 is defined as 20 percent improvement respectively in: a) swollen joint count (SJC) and tender joint count (TJC) and b) Three of the following 5 assessments: Subject's global assessment of pain by VAS Subject's global assessment of disease activity (VAS) Investigator/Physician's global assessment of disease activity (VAS) Subject's assessment of disability measured by HAQ-DI Acute phase reactant (ESR or CRP).

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

1015 participants

Primary outcome timeframe

Week 24

Results posted on

2020-11-27

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo × 2 IV + MTX Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.	Ocrelizumab 200 mg × 2 IV + MTX Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.
Overall Study STARTED	324	344	347
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	324	344	347

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo × 2 IV + MTX Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.	Ocrelizumab 200 mg × 2 IV + MTX Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.
Overall Study Death	3	1	4
Overall Study Protocol Violation	6	2	5
Overall Study Study Terminated by Sponsor	260	288	282
Overall Study Withdrawal by Subject	17	24	26
Overall Study Lack of Efficacy	12	1	6
Overall Study Non-Compliance with Study Drug	5	6	3
Overall Study Adverse Event	10	12	16
Overall Study Lost to Follow-up	11	10	5

Baseline Characteristics

A Study of Ocrelizumab Compared to Placebo in Patients With Active Rheumatoid Arthritis Continuing Methotrexate Treatment (STAGE)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo × 2 IV + MTX n=320 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.	Ocrelizumab 200 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Total n=1006 Participants Total of all reporting groups
Age, Continuous	50.5 Years STANDARD_DEVIATION 11.54 • n=5 Participants	51.8 Years STANDARD_DEVIATION 11.97 • n=7 Participants	50.9 Years STANDARD_DEVIATION 12.23 • n=5 Participants	51.1 Years STANDARD_DEVIATION 11.91 • n=4 Participants
Sex: Female, Male Female	248 Participants n=5 Participants	283 Participants n=7 Participants	282 Participants n=5 Participants	813 Participants n=4 Participants
Sex: Female, Male Male	72 Participants n=5 Participants	60 Participants n=7 Participants	61 Participants n=5 Participants	193 Participants n=4 Participants

PRIMARY outcome

Timeframe: Week 24

Population: ITT population included all randomised participants who had received any part of an infusion of study medication.

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=320 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24	56.9 Percentage of participants Interval 51.6 to 62.1	54.5 Percentage of participants Interval 49.2 to 59.8	35.7 Percentage of participants Interval 30.5 to 41.0

PRIMARY outcome

Timeframe: Week 48

Population: ITT population included all randomised participants who had received any part of an infusion of study medication.

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=320 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 48	58.3 Percentage of participants Interval 53.1 to 63.5	62.1 Percentage of participants Interval 57.0 to 67.2	27.6 Percentage of participants Interval 22.7 to 32.5

PRIMARY outcome

Timeframe: From baseline up to 8.5 years

Population: The safety population included all participants who were randomized and received any part of an infusion of study drug and provided at least one assessment of safety.

An AE was defined as any untoward medical occurrence in a subject administered a pharmaceutical product which does not necessarily have a causal relationship with the treatment. Pre-existing conditions which worsened during the study were also reported as AEs.

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=320 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Percentage of Participants With Adverse Events (AEs)	82.2 Percentage of participants	83.7 Percentage of participants	79.4 Percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: ITT population included all randomised participants who had received any part of an infusion of study medication.

ACR70 is defined as 70 percent improvement respectively in: a) swollen joint count (SJC) and tender joint count (TJC) and b) Three of the following 5 assessments: Subject's global assessment of pain by VAS Subject's global assessment of disease activity (VAS) Investigator/Physician's global assessment of disease activity (VAS) Subject's assessment of disability measured by HAQ-DI Acute phase reactant (ESR or CRP).

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=320 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Percentage of Participants With a Major Clinical Response (ACR70 for ≥ 6 Months) at Week 48	6.1 Percentage of participants Interval 3.6 to 8.7	7.3 Percentage of participants Interval 4.5 to 10.0	0.9 Percentage of participants Interval 0.0 to 2.0

SECONDARY outcome

Timeframe: Weeks 24 and 48

Population: ITT population included all randomised participants who had received any part of an infusion of study medication.

The Disease Activity Score (DAS28) 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 and Erythrocyte Sedimentation Rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=319 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Remission (DAS28 < 2.6) at Weeks 24 and 48 Week 24	7.9 Percentage of participants Interval 5.0 to 10.7	10.8 Percentage of participants Interval 7.5 to 14.1	5.3 Percentage of participants Interval 2.9 to 7.8
Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Remission (DAS28 < 2.6) at Weeks 24 and 48 Week 48	16.0 Percentage of participants Interval 12.2 to 19.9	17.5 Percentage of participants Interval 13.5 to 21.5	5.3 Percentage of participants Interval 2.9 to 7.8

SECONDARY outcome

Timeframe: Weeks 24 and 48

Population: ITT population included all randomised participants who had received any part of an infusion of study medication.

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=340 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=336 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=316 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Change From Baseline in DAS28 at Weeks 24 and 48 Baseline	6.40 Units on a Scale Standard Deviation 1.143	6.40 Units on a Scale Standard Deviation 1.077	6.42 Units on a Scale Standard Deviation 1.103
Change From Baseline in DAS28 at Weeks 24 and 48 Change at Week	-2.00 Units on a Scale Standard Deviation 1.248	-2.02 Units on a Scale Standard Deviation 1.310	-1.33 Units on a Scale Standard Deviation 1.329
Change From Baseline in DAS28 at Weeks 24 and 48 Change at Week 48	-2.42 Units on a Scale Standard Deviation 1.504	-2.68 Units on a Scale Standard Deviation 1.475	-1.38 Units on a Scale Standard Deviation 1.290

SECONDARY outcome

Timeframe: Weeks 24 and 48

Population: ITT population included all randomised participants who had received any part of an infusion of study medication.

DAS 28 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 and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement. EULAR Good response: DAS28 ≤ 3.2 and a change from Baseline \< -1.2. EULAR Moderate response: DAS28 \>3.2 to ≤ 5.1 or a change from Baseline \< -0.6 to ≥ -1.2.

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=320 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders) at Weeks 24 and 48 Week 24	68.8 Percentage of participants	70.0 Percentage of participants	41.6 Percentage of participants
European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders) at Weeks 24 and 48 Week 48	65.9 Percentage of participants	72.0 Percentage of participants	35.3 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 24 and 48

Population: ITT population included all randomised participants who had received any part of an infusion of study medication.

ACR50 is defined as 50 percent improvement respectively in: a) swollen joint count (SJC) and tender joint count (TJC) and b) Three of the following 5 assessments: Subject's global assessment of pain by VAS Subject's global assessment of disease activity (VAS) Investigator/Physician's global assessment of disease activity (VAS) Subject's assessment of disability measured by HAQ-DI Acute phase reactant (ESR or CRP).

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=319 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Percentage of Participants Achieving an ACR50 Response at Weeks 24 and 48 Week 24	31.8 Percentage of participants Interval 26.9 to 36.7	31.2 Percentage of participants Interval 26.3 to 36.1	16.3 Percentage of participants Interval 12.2 to 20.4
Percentage of Participants Achieving an ACR50 Response at Weeks 24 and 48 Week 48	39.9 Percentage of participants Interval 34.8 to 45.1	36.7 Percentage of participants Interval 31.6 to 41.8	12.9 Percentage of participants Interval 9.2 to 16.5

SECONDARY outcome

Timeframe: Weeks 24 and 48

Population: ITT population included all randomised participants who had received any part of an infusion of study medication.

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=319 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Percentage of Participants Achieving an ACR70 Response at Weeks 24 and 48 Week 24	14.3 Percentage of participants Interval 10.6 to 18.0	12.2 Percentage of participants Interval 8.8 to 15.7	5.6 Percentage of participants Interval 3.1 to 8.2
Percentage of Participants Achieving an ACR70 Response at Weeks 24 and 48 Week 48	20.7 Percentage of participants Interval 16.4 to 25.0	22.4 Percentage of participants Interval 18.0 to 26.9	6.6 Percentage of participants Interval 3.8 to 9.3

SECONDARY outcome

Timeframe: Baseline, Week 24, 48

Population: ITT population included all randomised participants who had received any part of an infusion of study medication.

66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66.

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=311 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=308 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=235 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Percent Change From Baseline in Swollen Joint Count (SJC) at Weeks 24 and 48 Change at Week 24	-51.82 Percentage of Change Standard Deviation 80.805	-54.76 Percentage of Change Standard Deviation 39.896	-38.20 Percentage of Change Standard Deviation 66.127
Percent Change From Baseline in Swollen Joint Count (SJC) at Weeks 24 and 48 Change at Week 48	-61.36 Percentage of Change Standard Deviation 44.414	-64.22 Percentage of Change Standard Deviation 65.234	-39.39 Percentage of Change Standard Deviation 59.184

SECONDARY outcome

Timeframe: Baseline, Weeks 24, 48

Population: ITT population included all randomised participants who had received any part of an infusion of study medication.

68 joints were assessed for tenderness and joints were classified as tender/not tender giving a total possible tender joint count score of 0 to 68.

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=311 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=308 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=235 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Change From Baseline in Tender Joint Count (TJC) at Weeks 24 and 48 Change at Week 24	-55.11 Tendor joins Standard Deviation 37.962	-51.07 Tendor joins Standard Deviation 49.700	-36.97 Tendor joins Standard Deviation 58.675
Change From Baseline in Tender Joint Count (TJC) at Weeks 24 and 48 Change at Week 48	-61.51 Tendor joins Standard Deviation 37.229	-59.55 Tendor joins Standard Deviation 48.474	-35.91 Tendor joins Standard Deviation 64.358

SECONDARY outcome

Timeframe: Baseline, Week 24, 48

Population: ITT population included all randomised participants who had received any part of an infusion of study medication.

The patient assessed their pain on a 0 to 100 millimeters (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change indicated improvement.

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=307 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=304 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=230 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Change From Baseline in Patient's Pain Visual Analogue Scale (VAS) at Weeks 24 and 48 Change at Week 24	-32.02 Units on scale Standard Deviation 88.637	-27.73 Units on scale Standard Deviation 139.732	-9.10 Units on scale Standard Deviation 109.646
Change From Baseline in Patient's Pain Visual Analogue Scale (VAS) at Weeks 24 and 48 Change at Week 48	-38.86 Units on scale Standard Deviation 104.267	-32.47 Units on scale Standard Deviation 197.692	-2.28 Units on scale Standard Deviation 148.933

SECONDARY outcome

Timeframe: Baseline, Week 24, 48

Population: ITT population included all randomised participants who had received any part of an infusion of study medication.

The physician's global assessment of disease activity is assessed on a 0 to 100 millimetres (mm) horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as "maximum disease activity" (maximum arthritis disease activity).

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=320 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Change From Baseline in Physician's Global VAS at Weeks 24 and 48 Change at Week 24	-51.44 Units on scale Standard Deviation 34.669	-53.02 Units on scale Standard Deviation 34.479	-40.23 Units on scale Standard Deviation 39.655
Change From Baseline in Physician's Global VAS at Weeks 24 and 48 Change at Week 48	-61.29 Units on scale Standard Deviation 31.543	-62.10 Units on scale Standard Deviation 30.866	-41.60 Units on scale Standard Deviation 43.285

SECONDARY outcome

Timeframe: Baseline, Week 24, 48

Population: ITT population included all randomised participants who had received any part of an infusion of study medication.

The patient's global assessment of disease activity is assessed on a 0 to 100 millimeters (mm) horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=308 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=303 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=231 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Change From Baseline in Patient's Global VAS at Weeks 24 and 48 Change at Week 24	-37.96 Units on scale Standard Deviation 83.908	-36.99 Units on scale Standard Deviation 79.130	-20.73 Units on scale Standard Deviation 74.480
Change From Baseline in Patient's Global VAS at Weeks 24 and 48 Change at Week 48	-42.02 Units on scale Standard Deviation 103.526	-55.26 Units on scale Standard Deviation 37.873	-17.13 Units on scale Standard Deviation 100.706

SECONDARY outcome

Timeframe: Baseline, Week 24, 48

Population: ITT population included all randomised participants who had received any part of an infusion of study medication.

The serum concentration of C-Reactive Protein (CRP) is measured in milligrams per deciliter (mg/dL). A reduction in the level is considered an improvement.

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=311 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=308 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=235 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Change From Baseline in C-Reactive Protein (CRP) at Weeks 24 and 48 Change at Week 48	-40.89 Milligrams per deciliter (mg/dL) Standard Deviation 90.139	15.14 Milligrams per deciliter (mg/dL) Standard Deviation 820.007	22.01 Milligrams per deciliter (mg/dL) Standard Deviation 190.346
Change From Baseline in C-Reactive Protein (CRP) at Weeks 24 and 48 Change at Week 24	-30.41 Milligrams per deciliter (mg/dL) Standard Deviation 109.193	-23.07 Milligrams per deciliter (mg/dL) Standard Deviation 109.193	11.64 Milligrams per deciliter (mg/dL) Standard Deviation 116.697

SECONDARY outcome

Timeframe: Baseline, Week 24, 48

Population: ITT population included all randomised participants who had received any part of an infusion of study medication. Here, 'n' signifies the number of partcipants evaluated at a specified time point.

HAQ-DI is a self-completed patient questionnaire specific for Rheumatoid Arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. Calculate HAQ-DI the patient must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=320 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Change From Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) at Weeks 24 and 48 Change at Week 24	-30.12 Percentage Change from Baseline Standard Deviation 86.217	-40.83 Percentage Change from Baseline Standard Deviation 38.243	-20.11 Percentage Change from Baseline Standard Deviation 48.921
Change From Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) at Weeks 24 and 48 Change at Week 48	-35.47 Percentage Change from Baseline Standard Deviation 78.670	-45.63 Percentage Change from Baseline Standard Deviation 39.241	-22.67 Percentage Change from Baseline Standard Deviation 57.893

SECONDARY outcome

Timeframe: Baseline, Week 24, 48

Population: ITT population included all randomised participants who had received any part of an infusion of study medication. Here, 'n' signifies the number of participants evaluated at a specified time point.

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=311 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=308 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=234 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Change From Baseline in the Erythrocyte Sedimentation Rate (ESR) at Weeks 24 and 48 Change at Week 48	-27.24 Percentage Change from Baseline Standard Deviation 147.973	-41.19 Percentage Change from Baseline Standard Deviation 55.485	-2.72 Percentage Change from Baseline Standard Deviation 57.893
Change From Baseline in the Erythrocyte Sedimentation Rate (ESR) at Weeks 24 and 48 Change at Week 24	-20.10 Percentage Change from Baseline Standard Deviation 90.059	-29.98 Percentage Change from Baseline Standard Deviation 57.195	-2.51 Percentage Change from Baseline Standard Deviation 66.453

SECONDARY outcome

Timeframe: Baseline, Week 24, 48

Population: mITT population. Number of participants analysed signifies participants who were evaluated for the endpoint.

mTSS: measure of joint damage that combines scores for bone erosion and joint space narrowing (JNS). Erosion score: total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=normal to 3.5=very severe erosion. JNS score: total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=normal to 4.0=definite ankylosis (stiffness or fixation of a joint). mTSS scores ranged from 0 (normal) to 292 (worst possible total score). Change= mTSS score at Week 24 minus score at baseline. An increase in mTSS from baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=322 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=320 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=305 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Change From Baseline in the Modified Total Sharp Score (mTSS) at Weeks 24 and 48 Baseline	31.45 Units on scale Standard Deviation 51.323	31.99 Units on scale Standard Deviation 49.602	33.58 Units on scale Standard Deviation 51.106
Change From Baseline in the Modified Total Sharp Score (mTSS) at Weeks 24 and 48 Change at Week 24	0.34 Units on scale Standard Deviation 2.424	-0.03 Units on scale Standard Deviation 2.534	1.04 Units on scale Standard Deviation 2.842
Change From Baseline in the Modified Total Sharp Score (mTSS) at Weeks 24 and 48 Change at Week 48	0.26 Units on scale Standard Deviation 2.791	-0.03 Units on scale Standard Deviation 2.911	1.74 Units on scale Standard Deviation 5.293

SECONDARY outcome

Timeframe: Baseline, Week 24, 48

Population: mITT population included all participants who were in the ITT analysis set and had both baseline radiograph and at least one post-baseline radiograph for campaign 1. Here, the number of participants analysed signifies participants who were evaluated for the endpoint.

The erosion score is a summary of erosion severity in 32 joints of the hands (16 joints per hand) and 12 joints in the feet (6 joints per foot). Each joint is scored, according to the surface area involved, from 0 to 5, with 5 indicating extensive loss of bone from more than one-half of the articulating bone (0 indicates no erosion). Because each side of a foot joint is graded separately on this scale, the maximum erosion score for a foot joint is 10. The maximal erosion score is 280.

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=322 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=329 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=305 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Change From Baseline in Modified Erosion Score at Weeks 24 and 48 Baseline	16.22 Units on scale Standard Deviation 27.875	16.24 Units on scale Standard Deviation 26.103	17.10 Units on scale Standard Deviation 27.256
Change From Baseline in Modified Erosion Score at Weeks 24 and 48 Change at Week 24	0.18 Units on scale Standard Deviation 1.487	0.04 Units on scale Standard Deviation 1.511	0.61 Units on scale Standard Deviation 1.778
Change From Baseline in Modified Erosion Score at Weeks 24 and 48 Change at week 48	0.08 Units on scale Standard Deviation 1.690	-0.08 Units on scale Standard Deviation 1.588	1.06 Units on scale Standard Deviation 3.238

SECONDARY outcome

Timeframe: Baseline, Week 24, 48

The joint space narrowing score summarizes the severity of joint space narrowing in 30 joints of the hands and 12 joints of the feet. Assessment of joint space narrowing for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, is scored from 0 to 4, with 0 indicating no/normal joint space narrowing and 4 indicating complete loss of joint space, bony ankylosis, or luxation. The maximum joint space narrowing score is 168.

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=322 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=329 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=305 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Change From Baseline in Modified Joint Space Narrowing Score at Weeks 24 and 48 Baseline	15.22 Units on scale Standard Deviation 25.012	15.75 Units on scale Standard Deviation 25.118	16.47 Units on scale Standard Deviation 25.990
Change From Baseline in Modified Joint Space Narrowing Score at Weeks 24 and 48 Change at Week 24	0.16 Units on scale Standard Deviation 1.655	-0.07 Units on scale Standard Deviation 1.504	0.43 Units on scale Standard Deviation 1.654
Change From Baseline in Modified Joint Space Narrowing Score at Weeks 24 and 48 Change at Week 48	0.18 Units on scale Standard Deviation 1.471	0.05 Units on scale Standard Deviation 1.859	0.68 Units on scale Standard Deviation 2.777

SECONDARY outcome

Timeframe: Weeks 24, 48

Population: The modified Intent-to-Treat (mITT) population included all participants who were in the ITT analysis set and had both baseline radiograph and at least one post-baseline radiograph for campaign 1. Here, the number of participants analysed signifies subjects who were evaluated for the endpoint.

Radiographic progression was defined as a change of ≤ 0 in the total Genant-modified Sharp score. The Genant-modified Sharp scoring system assesses structural damage due to rheumatoid arthritis in radiographs. A score for erosions of 0-3.5 (8 gradations) is assigned for 14 joints in each hand and wrist, and 6 joints in each foot. Joint space narrowing scores of 0-4 (9 gradations) are assigned to 13 joints in each hand and 6 joints in each foot. The maximum erosion score is 40 x 3.5 = 140. The maximum joint space narrowing score is 38 x 4.0 = 152. Both the erosion and joint space narrowing scores are normalized to 145 and are added together for a maximum total Genant-modified Sharp score of 290; the minimum score is 0. A higher score indicates more damage.

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=322 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=329 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=305 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Percentage of Participants Without Radiographic Progression Defined as Change in mTSS ≤ 0 at Weeks 24 and 48 Week 24	58.7 Percentage of Participants Interval 53.3 to 64.1	65.3 Percentage of Participants Interval 60.2 to 70.5	47.5 Percentage of Participants Interval 41.9 to 53.1
Percentage of Participants Without Radiographic Progression Defined as Change in mTSS ≤ 0 at Weeks 24 and 48 Week 48	58.7 Percentage of Participants Interval 53.3 to 64.1	60.8 Percentage of Participants Interval 55.5 to 66.1	37.7 Percentage of Participants Interval 32.3 to 43.1

SECONDARY outcome

Timeframe: Baseline, Week 48

Population: mITT population. Number of participants analysed signifies participants who were evaluated for the endpoint.

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=322 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=329 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=305 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Percentage of Participants With a Reduction in Modified Total Sharp Score (mTSS) From Baseline at Week 48	22.7 Percentage of Participants Interval 18.1 to 27.2	29.8 Percentage of Participants Interval 24.8 to 34.7	11.8 Percentage of Participants Interval 8.2 to 15.4

SECONDARY outcome

Timeframe: Week 24, 48

Population: ITT population included all randomised participants who had received any part of an infusion of study medication. Here, the number of participants analysed signifies participants evaluated for this endpoint.

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=343 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=319 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Percentage of Participants With a Reduction of Greater Than or Equal to 0.25 Units in the HAQ-DI Score at Weeks 24 and Week 24	59.8 Percentage of Participants Interval 54.6 to 65.0	66.5 Percentage of Participants Interval 61.5 to 71.5	42.3 Percentage of Participants Interval 36.9 to 47.7
Percentage of Participants With a Reduction of Greater Than or Equal to 0.25 Units in the HAQ-DI Score at Weeks 24 and Week 48	58.9 Percentage of Participants Interval 53.7 to 64.1	65.9 Percentage of Participants Interval 60.9 to 70.9	34.8 Percentage of Participants Interval 29.6 to 40.0

SECONDARY outcome

Timeframe: Baseline, Week 24, 48

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 and Mental 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	Ocrelizumab 200 mg × 2 IV + MTX n=334 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=334 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=312 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Change From Baseline in Short Form Health Survey (SF-36) Subscale and Summary Scores at Weeks 24 and 48 Baseline: Mental Component Summary	39.99 Units on scale Standard Deviation 11.863	40.48 Units on scale Standard Deviation 12.822	40.54 Units on scale Standard Deviation 12.282
Change From Baseline in Short Form Health Survey (SF-36) Subscale and Summary Scores at Weeks 24 and 48 Change at Week 24: Mental Component Summary	6.11 Units on scale Standard Deviation 10.082	5.80 Units on scale Standard Deviation 11.224	4.38 Units on scale Standard Deviation 10.886
Change From Baseline in Short Form Health Survey (SF-36) Subscale and Summary Scores at Weeks 24 and 48 Change at Week 48: Mental Component Summary	6.36 Units on scale Standard Deviation 10.212	6.43 Units on scale Standard Deviation 11.795	4.15 Units on scale Standard Deviation 10.326
Change From Baseline in Short Form Health Survey (SF-36) Subscale and Summary Scores at Weeks 24 and 48 Baseline: Physical Component Summary	32.24 Units on scale Standard Deviation 7.401	31.58 Units on scale Standard Deviation 8.039	31.86 Units on scale Standard Deviation 7.387
Change From Baseline in Short Form Health Survey (SF-36) Subscale and Summary Scores at Weeks 24 and 48 Change at Week 24: Physical Component Summary	6.73 Units on scale Standard Deviation 8.385	7.71 Units on scale Standard Deviation 7.328	5.29 Units on scale Standard Deviation 8.421
Change From Baseline in Short Form Health Survey (SF-36) Subscale and Summary Scores at Weeks 24 and 48 Change at Week 48: Physical Component Summary	8.38 Units on scale Standard Deviation 8.347	9.15 Units on scale Standard Deviation 8.389	5.28 Units on scale Standard Deviation 8.373

SECONDARY outcome

Timeframe: Baseline, Week 24, 48

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

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=340 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=340 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=317 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Fatigue Assessment at Weeks 24 and 48 Baseline	26.87 Units on scale Standard Deviation 10.920	26.57 Units on scale Standard Deviation 11.194	27.25 Units on scale Standard Deviation 10.821
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Fatigue Assessment at Weeks 24 and 48 Change at Week 24	7.18 Units on scale Standard Deviation 9.755	7.07 Units on scale Standard Deviation 10.269	5.14 Units on scale Standard Deviation 9.864
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Fatigue Assessment at Weeks 24 and 48 Change at Week 48	8.01 Units on scale Standard Deviation 10.132	8.41 Units on scale Standard Deviation 10.682	5.39 Units on scale Standard Deviation 10.054

SECONDARY outcome

Timeframe: Baseline, Week 24, 48

The modified BPI (short-form) is a short questionnaire to assess the severity of pain and the impact of pain on daily functions. The first two questions relate to average and current pain respectively and are assessed on a scale from 0 to 10, where 0 represents no pain, and 10 represents pain as bad as one can imagine. The degree to which pain has interfered with 7 different aspects is also rated on a scale from 0 to 10, where 0 represents that pain does not interfere and 10 that pain completely interferes.

Outcome measures

Outcome measures
Measure	Ocrelizumab 200 mg × 2 IV + MTX n=340 Participants Participants received two IV infusion of ocrelizumab 200 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Ocrelizumab 500 mg × 2 IV + MTX n=335 Participants Participants received two IV infusion of ocrelizumab 500 mg on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 mg was administered weekly.	Placebo × 2 IV + MTX n=316 Participants Participants received two intravenous (IV) infusion matching placebo to ocrelizumab on Day 1 and Day 15. A repeat course was administered at Weeks 24 and 26. Methotrexate 7.5-25 milligram (mg) was administered weekly.
Change From Baseline in Pain Quality and Impact of Pain on Daily Function Measured by the Brief Pain Inventory (BPI) Short Form at Weeks 24 and 48 Baseline: average pain	6.28 Units on scale Standard Deviation 2.077	6.42 Units on scale Standard Deviation 2.194	6.39 Units on scale Standard Deviation 2.011
Change From Baseline in Pain Quality and Impact of Pain on Daily Function Measured by the Brief Pain Inventory (BPI) Short Form at Weeks 24 and 48 Baseline: pain right now	5.75 Units on scale Standard Deviation 2.495	5.82 Units on scale Standard Deviation 2.533	5.57 Units on scale Standard Deviation 2.398
Change From Baseline in Pain Quality and Impact of Pain on Daily Function Measured by the Brief Pain Inventory (BPI) Short Form at Weeks 24 and 48 Change at Week 24: average pain	-2.45 Units on scale Standard Deviation 2.299	-2.48 Units on scale Standard Deviation 2.424	-1.82 Units on scale Standard Deviation 2.441
Change From Baseline in Pain Quality and Impact of Pain on Daily Function Measured by the Brief Pain Inventory (BPI) Short Form at Weeks 24 and 48 Change at Week 24: pain right now	-2.32 Units on scale Standard Deviation 2.659	-2.24 Units on scale Standard Deviation 2.671	-1.57 Units on scale Standard Deviation 2.775
Change From Baseline in Pain Quality and Impact of Pain on Daily Function Measured by the Brief Pain Inventory (BPI) Short Form at Weeks 24 and 48 Change at Week 48: average pain	-2.92 Units on scale Standard Deviation 2.442	-3.06 Units on scale Standard Deviation 2.422	-1.78 Units on scale Standard Deviation 2.619
Change From Baseline in Pain Quality and Impact of Pain on Daily Function Measured by the Brief Pain Inventory (BPI) Short Form at Weeks 24 and 48 Change at Week 48: pain right now	-2.66 Units on scale Standard Deviation 2.676	-2.92 Units on scale Standard Deviation 2.681	-1.53 Units on scale Standard Deviation 2.795

Adverse Events

Placebo × 2 IV + MTX

Serious events: 73 serious events

Other events: 228 other events

Deaths: 5 deaths

Ocrelizumab 200 mg × 2 IV + MTX

Serious events: 61 serious events

Other events: 272 other events

Deaths: 2 deaths

Ocrelizumab 500 mg × 2 IV + MTX

Serious events: 78 serious events

Other events: 273 other events

Deaths: 8 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

F. Hoffmann-La Roche Ltd

Phone: +41 616878333

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