Rheumatoid Arthritis
Conditions
Keywords
RA, SCRIPT, anti-CD20, CD20
Brief summary
This study will evaluate the efficacy and safety of ocrelizumab, compared with placebo, in patients with active rheumatoid arthritis who have an inadequate response to at least one anti-TNF-alpha therapy. Patients will be randomized to receive placebo, 200mg of intravenous ocrelizumab, or 500mg of i.v. ocrelizumab on days 1 and 15. A repeat course of i.v. treatment will be administered at weeks 24 and 26. All patients will receive stable doses of either concomitant methotrexate (7.5-25mg/week) or leflunomide (10-20mg po daily) and may receive additional DMARDs. The treatment period is planned for 48 weeks (until primary analysis) and then participants will enter the open label phase until the drug is commercialized. Target sample size is 1000.
Interventions
DRUGLeflunomide
Oral repeating dose
DRUGMethotrexate
Oral or parenteral repeating dose
DRUGOcrelizumab
Intravenous repeating dose (200mg)
DRUGPlacebo
Intravenous repeating dose
Sponsors
Roche Pharma AG
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients, ≥ 18 years of age * Rheumatoid arthritis for at least 3 months * Inadequate response to previous or current treatment with at least one anti-TNF-alpha agent * Receiving either leflunomide or methotrexate for ≥ 12 weeks, with a stable dose for the last 4 weeks * Swollen joint count (SJC) ≥ 4 (66 joint count) and tender joint count (TJC) ≥ 4 (68 joint count) at screening and baseline. * CRP ≥ 0.6 mg/dL using a high-sensitivity assay. * Positive rheumatoid factor or positive anti-CCP antibody or both.
Exclusion criteria
* Rheumatic autoimmune disease or inflammatory joint disease, other than RA * Any surgical procedure in past 12 weeks,or planned within 48 weeks of baseline
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With American College of Rheumatology 20 (ACR20) Responses | Weeks 24 and 48 | ACR20 response: greater than or equal to (≥) 20% improvement in tender or swollen joint counts and 20% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) participant assessment of disease activity, 3) Patient Assessment of Pain (visual analog scale \[VAS\]), 4) participant assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) erythrocyte sedimentation rate (ESR) at each visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Disease Activity Score (DAS28) Remission | Weeks 24 and 48 | The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6. |
| Change in DAS28 From Baseline | Weeks 24 and 48 | The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. |
| Percentage of Participants With EULAR Response Rates of Good/ Moderate | Weeks 24 and 48 | The EULAR response rate was based on the assessment of disease activity using the DAS28. The EULAR response criteria included not only change in disease activity but current disease activity. To be classified as responders, participants had to have a significant change in DAS28 and a low current disease activity. There were 4 categories of EULAR response rates: good, moderate, good/moderate, and none. |
| Percentage of Participants With a Major Clinical Response | Week 48 | Major clinical response was defined as achieving an ACR70 response and maintaining this response for a consecutive period of at least 6 months. |
| Percentage of Participants Achieving an ACR70 Response | Weeks 24 and 48 | ACR70 response is defined as a ≥ 70% improvement (reduction) compared with Baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: physician's global assessment of disease activity (MDG), patient's global assessment of disease activity (PGA), patient's assessment of pain, HAQ-DI and CRP. |
| Percentage of Participants With a Reduction in the HAQ-DI Score | Weeks 24 and 48 | Health Assessment Questionnaire - Disability Index (HAQ-DI): The Stanford Health Assessment Questionnaire disability index is a patient reported questionnaire specific for RA. It consists of 20 questions referring to eight component. Reduction in the HAQ-DI score of 0.25 units from baseline to weeks 24 and 48 represented a minimal clinically relevant improvement. |
| Percentage of Participants Achieving an ACR50 Response | Weeks 24 and 48 | ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: physician's global assessment of disease activity (MDG), patient's global assessment of disease activity (PGA), patient's assessment of pain, Health Assessment Questionnaire with Disability Index (HAQ-DI), and C-Reactive Protein (CRP). |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Czechia, France, Germany, Hungary, Israel, Italy, Japan, Mexico, Netherlands, New Zealand, Panama, Peru, Poland, Slovakia, Slovenia, Spain, Sweden, Switzerland, Taiwan, United States
Participant flow
Recruitment details
Participants were recruited across 25 countries.
Pre-assignment details
The study population comprised of adult participants with active RA of \>/= 3 months duration who had an inadequate clinical response due to toxicity or inadequate efficacy to previous or current treatment with one or more anti-TNF-alpha therapies.
Participants by arm
| Arm | Count |
|---|---|
| Placebo x 2 IV + Non-Biologic DMARD Participants received Ocrelizumab matching placebo intravenously (IV) in two infusions, separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD | 277 |
| Ocrelizumab 200 mg x 2 + Non-Biologic DMARD Participants received 2 intravenous (IV) infusions of 200 milligram (mg) of ocrelizumab (total 400 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD | 277 |
| Ocrelizumab 500 mg x 2 + Non-Biologic DMARD Participants received 2 intravenous (IV) infusions of 500 milligram (mg) of ocrelizumab (total 1000 mg), separated by 14 days (Day 1 and Day 15) in combination with any non-biologic DMARD | 282 |
| Total | 836 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Blinded Treatment Phase (up to Week 48) | Adverse Event | 11 | 13 | 7 | 0 |
| Blinded Treatment Phase (up to Week 48) | Death | 2 | 1 | 1 | 0 |
| Blinded Treatment Phase (up to Week 48) | Early termination of the study | 24 | 20 | 21 | 0 |
| Blinded Treatment Phase (up to Week 48) | Lack of Efficacy | 22 | 5 | 6 | 0 |
| Blinded Treatment Phase (up to Week 48) | Lost to Follow-up | 0 | 4 | 3 | 0 |
| Blinded Treatment Phase (up to Week 48) | Non-Compliance with Study Drug | 0 | 2 | 0 | 0 |
| Blinded Treatment Phase (up to Week 48) | Protocol Violation | 1 | 3 | 0 | 0 |
| Blinded Treatment Phase (up to Week 48) | Withdrawal by Subject | 12 | 7 | 7 | 0 |
| OLE Phase (From Week 48) | Adverse Event | 0 | 0 | 0 | 8 |
| OLE Phase (From Week 48) | Death | 0 | 0 | 0 | 7 |
| OLE Phase (From Week 48) | Early termination of the study | 0 | 0 | 0 | 578 |
| OLE Phase (From Week 48) | Lack of Efficacy | 0 | 0 | 0 | 13 |
| OLE Phase (From Week 48) | Lost to Follow-up | 0 | 0 | 0 | 4 |
| OLE Phase (From Week 48) | Non-Compliance with Study Drug | 0 | 0 | 0 | 4 |
| OLE Phase (From Week 48) | Withdrawal by Subject | 0 | 0 | 0 | 50 |
Baseline characteristics
| Characteristic | Placebo x 2 IV + Non-Biologic DMARD | Ocrelizumab 200 mg x 2 + Non-Biologic DMARD | Ocrelizumab 500 mg x 2 + Non-Biologic DMARD | Total |
|---|---|---|---|---|
| Age, Continuous | 54.1 years STANDARD_DEVIATION 11.3 | 54.5 years STANDARD_DEVIATION 11.2 | 53.8 years STANDARD_DEVIATION 11.6 | 54.2 years STANDARD_DEVIATION 11.3 |
| Race/Ethnicity, Customized American indian or Alaska native | 9 Participants | 8 Participants | 9 Participants | 26 Participants |
| Race/Ethnicity, Customized Asian (Indian Subcontinent) | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian (Other than Indian subcontinent) | 39 Participants | 38 Participants | 38 Participants | 115 Participants |
| Race/Ethnicity, Customized Black | 16 Participants | 18 Participants | 12 Participants | 46 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 6 Participants | 11 Participants | 14 Participants | 31 Participants |
| Race/Ethnicity, Customized White | 206 Participants | 201 Participants | 207 Participants | 614 Participants |
| Sex: Female, Male Female | 215 Participants | 214 Participants | 236 Participants | 665 Participants |
| Sex: Female, Male Male | 62 Participants | 63 Participants | 46 Participants | 171 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 276 | 2 / 276 | 4 / 284 | 11 / 664 |
| other Total, other adverse events | 152 / 276 | 153 / 276 | 158 / 284 | 361 / 664 |
| serious Total, serious adverse events | 41 / 276 | 46 / 276 | 40 / 284 | 138 / 664 |
Outcome results
Primary
Percentage of Participants With American College of Rheumatology 20 (ACR20) Responses
ACR20 response: greater than or equal to (≥) 20% improvement in tender or swollen joint counts and 20% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) participant assessment of disease activity, 3) Patient Assessment of Pain (visual analog scale \[VAS\]), 4) participant assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) erythrocyte sedimentation rate (ESR) at each visit.
Time frame: Weeks 24 and 48
Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo x 2 IV + Non-Biologic DMARD | Percentage of Participants With American College of Rheumatology 20 (ACR20) Responses | Percentage of Responders at Week 24 | 22 Percentage |
| Placebo x 2 IV + Non-Biologic DMARD | Percentage of Participants With American College of Rheumatology 20 (ACR20) Responses | Percentage of Responders at Week 48 | 19.5 Percentage |
| Ocrelizumab 200 mg x 2 + Non-Biologic DMARD | Percentage of Participants With American College of Rheumatology 20 (ACR20) Responses | Percentage of Responders at Week 24 | 42.2 Percentage |
| Ocrelizumab 200 mg x 2 + Non-Biologic DMARD | Percentage of Participants With American College of Rheumatology 20 (ACR20) Responses | Percentage of Responders at Week 48 | 48.7 Percentage |
| Ocrelizumab 500 mg x 2 + Non-Biologic DMARD | Percentage of Participants With American College of Rheumatology 20 (ACR20) Responses | Percentage of Responders at Week 48 | 50.7 Percentage |
| Ocrelizumab 500 mg x 2 + Non-Biologic DMARD | Percentage of Participants With American College of Rheumatology 20 (ACR20) Responses | Percentage of Responders at Week 24 | 47.9 Percentage |
Comparison: At Week 24, analysis was stratified by region and baseline DMARD therapyp-value: <0.000195% CI: [12.8, 27.9]Cochran-Mantel-Haenszel
Comparison: At Week 24, analysis was stratified by region and baseline DMARD therapyp-value: <0.000195% CI: [17.7, 32.7]Cochran-Mantel-Haenszel
Comparison: At Week 48, analysis was stratified by region and baseline DMARD therapyp-value: <0.000195% CI: [21.6, 36.6]Cochran-Mantel-Haenszel
Comparison: At Week 48, analysis was stratified by region and baseline DMARD therapyp-value: <0.000195% CI: [22.8, 37.7]Cochran-Mantel-Haenszel
Secondary
Change in DAS28 From Baseline
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10.
Time frame: Weeks 24 and 48
Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis Number of participants for whom data were collected is indicated for each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo x 2 IV + Non-Biologic DMARD | Change in DAS28 From Baseline | Week 24 | -0.99 Score on a scale | Standard Deviation 1.166 |
| Placebo x 2 IV + Non-Biologic DMARD | Change in DAS28 From Baseline | Baseline | 6.50 Score on a scale | Standard Deviation 1.014 |
| Placebo x 2 IV + Non-Biologic DMARD | Change in DAS28 From Baseline | Week 48 | -1.13 Score on a scale | Standard Deviation 1.404 |
| Ocrelizumab 200 mg x 2 + Non-Biologic DMARD | Change in DAS28 From Baseline | Week 24 | -1.60 Score on a scale | Standard Deviation 1.307 |
| Ocrelizumab 200 mg x 2 + Non-Biologic DMARD | Change in DAS28 From Baseline | Baseline | 6.47 Score on a scale | Standard Deviation 1.217 |
| Ocrelizumab 200 mg x 2 + Non-Biologic DMARD | Change in DAS28 From Baseline | Week 48 | -2.11 Score on a scale | Standard Deviation 1.348 |
| Ocrelizumab 500 mg x 2 + Non-Biologic DMARD | Change in DAS28 From Baseline | Baseline | 6.44 Score on a scale | Standard Deviation 1.039 |
| Ocrelizumab 500 mg x 2 + Non-Biologic DMARD | Change in DAS28 From Baseline | Week 48 | -2.38 Score on a scale | Standard Deviation 1.496 |
| Ocrelizumab 500 mg x 2 + Non-Biologic DMARD | Change in DAS28 From Baseline | Week 24 | -1.91 Score on a scale | Standard Deviation 1.349 |
Comparison: Week 24 analysis using adjusted mean difference. Model contains region, baseline DMARD therapy, baseline DAS28 score and treatmentp-value: <0.000195% CI: [-0.8, -0.3]Analysis of Variance
Comparison: Week 24 analysis using adjusted mean difference. Model contains region, baseline DMARD therapy, baseline DAS28 score and treatmentp-value: <0.000195% CI: [-1.1, -0.6]Analysis of Variance
Comparison: Week 48 analysis using adjusted mean difference. Model contains region, baseline DMARD therapy, baseline DAS28 score and treatmentp-value: <0.000195% CI: [-1.2, -0.7]Analysis of Variance
Comparison: Week 48 analysis using adjusted mean difference. Model contains region, baseline DMARD therapy, baseline DAS28 score and treatmentp-value: <0.000195% CI: [-1.5, -0.9]Analysis of Variance
Secondary
Percentage of Participants Achieving an ACR50 Response
ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: physician's global assessment of disease activity (MDG), patient's global assessment of disease activity (PGA), patient's assessment of pain, Health Assessment Questionnaire with Disability Index (HAQ-DI), and C-Reactive Protein (CRP).
Time frame: Weeks 24 and 48
Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo x 2 IV + Non-Biologic DMARD | Percentage of Participants Achieving an ACR50 Response | Percentage of Participants at Week 24 | 7.9 Percentage |
| Placebo x 2 IV + Non-Biologic DMARD | Percentage of Participants Achieving an ACR50 Response | Percentage of Participants at Week 48 | 9 Percentage |
| Ocrelizumab 200 mg x 2 + Non-Biologic DMARD | Percentage of Participants Achieving an ACR50 Response | Percentage of Participants at Week 24 | 21.3 Percentage |
| Ocrelizumab 200 mg x 2 + Non-Biologic DMARD | Percentage of Participants Achieving an ACR50 Response | Percentage of Participants at Week 48 | 28.5 Percentage |
| Ocrelizumab 500 mg x 2 + Non-Biologic DMARD | Percentage of Participants Achieving an ACR50 Response | Percentage of Participants at Week 24 | 24.8 Percentage |
| Ocrelizumab 500 mg x 2 + Non-Biologic DMARD | Percentage of Participants Achieving an ACR50 Response | Percentage of Participants at Week 48 | 30.9 Percentage |
Comparison: At Week 24, analysis was stratified by region and baseline DMARD therapyp-value: <0.000195% CI: [7.4, 19.1]Cochran-Mantel-Haenszel
Comparison: At Week 24, analysis was stratified by region and baseline DMARD therapyp-value: <0.000195% CI: [10.2, 22.1]Cochran-Mantel-Haenszel
Comparison: At Week 48, analysis was stratified by region and baseline DMARD therapyp-value: <0.000195% CI: [12.9, 25.6]Cochran-Mantel-Haenszel
Comparison: At Week 48, analysis was stratified by region and baseline DMARD therapyp-value: <0.000195% CI: [14.5, 27.1]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving an ACR70 Response
ACR70 response is defined as a ≥ 70% improvement (reduction) compared with Baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: physician's global assessment of disease activity (MDG), patient's global assessment of disease activity (PGA), patient's assessment of pain, HAQ-DI and CRP.
Time frame: Weeks 24 and 48
Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo x 2 IV + Non-Biologic DMARD | Percentage of Participants Achieving an ACR70 Response | Percentage of Participants at Week 24 | 2.9 Percentage |
| Placebo x 2 IV + Non-Biologic DMARD | Percentage of Participants Achieving an ACR70 Response | Percentage of Participants at Week 48 | 4.3 Percentage |
| Ocrelizumab 200 mg x 2 + Non-Biologic DMARD | Percentage of Participants Achieving an ACR70 Response | Percentage of Participants at Week 24 | 7.6 Percentage |
| Ocrelizumab 200 mg x 2 + Non-Biologic DMARD | Percentage of Participants Achieving an ACR70 Response | Percentage of Participants at Week 48 | 11.2 Percentage |
| Ocrelizumab 500 mg x 2 + Non-Biologic DMARD | Percentage of Participants Achieving an ACR70 Response | Percentage of Participants at Week 24 | 9.9 Percentage |
| Ocrelizumab 500 mg x 2 + Non-Biologic DMARD | Percentage of Participants Achieving an ACR70 Response | Percentage of Participants at Week 48 | 18.1 Percentage |
Comparison: At Week 24, analysis was stratified by region and baseline DMARD therapyp-value: 0.020395% CI: [0.7, 8.5]Cochran-Mantel-Haenszel
Comparison: At Week 24, analysis was stratified by region and baseline DMARD therapyp-value: 0.001495% CI: [2.6, 10.8]Cochran-Mantel-Haenszel
Comparison: At Week 48, analysis was stratified by region and baseline DMARD therapyp-value: 0.004295% CI: [2.1, 11.2]Cochran-Mantel-Haenszel
Comparison: At Week 48, analysis was stratified by region and baseline DMARD therapyp-value: <0.000195% CI: [8.2, 18.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving Disease Activity Score (DAS28) Remission
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score \< 2.6.
Time frame: Weeks 24 and 48
Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo x 2 IV + Non-Biologic DMARD | Percentage of Participants Achieving Disease Activity Score (DAS28) Remission | Percentage of Participants at Week 24 | 1.8 Percentage |
| Placebo x 2 IV + Non-Biologic DMARD | Percentage of Participants Achieving Disease Activity Score (DAS28) Remission | Percentage of Participants at Week 48 | 1.4 Percentage |
| Ocrelizumab 200 mg x 2 + Non-Biologic DMARD | Percentage of Participants Achieving Disease Activity Score (DAS28) Remission | Percentage of Participants at Week 24 | 5.8 Percentage |
| Ocrelizumab 200 mg x 2 + Non-Biologic DMARD | Percentage of Participants Achieving Disease Activity Score (DAS28) Remission | Percentage of Participants at Week 48 | 11.9 Percentage |
| Ocrelizumab 500 mg x 2 + Non-Biologic DMARD | Percentage of Participants Achieving Disease Activity Score (DAS28) Remission | Percentage of Participants at Week 48 | 12.1 Percentage |
| Ocrelizumab 500 mg x 2 + Non-Biologic DMARD | Percentage of Participants Achieving Disease Activity Score (DAS28) Remission | Percentage of Participants at Week 24 | 6.0 Percentage |
Comparison: At Week 24, analysis was stratified by region and baseline DMARD therapyp-value: 0.017595% CI: [0.7, 7.6]Cochran-Mantel-Haenszel
Comparison: At Week 24, analysis was stratified by region and baseline DMARD therapyp-value: 0.013495% CI: [0.9, 7.8]Cochran-Mantel-Haenszel
Comparison: At Week 48, analysis was stratified by region and baseline DMARD therapyp-value: <0.000195% CI: [6.2, 14.8]Cochran-Mantel-Haenszel
Comparison: At Week 48, analysis was stratified by region and baseline DMARD therapyp-value: <0.000195% CI: [6.2, 14.7]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With a Major Clinical Response
Major clinical response was defined as achieving an ACR70 response and maintaining this response for a consecutive period of at least 6 months.
Time frame: Week 48
Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo x 2 IV + Non-Biologic DMARD | Percentage of Participants With a Major Clinical Response | 1.8 Percentage |
| Ocrelizumab 200 mg x 2 + Non-Biologic DMARD | Percentage of Participants With a Major Clinical Response | 4.0 Percentage |
| Ocrelizumab 500 mg x 2 + Non-Biologic DMARD | Percentage of Participants With a Major Clinical Response | 5.7 Percentage |
Comparison: Analysis was stratified by region and baseline DMARD therapyp-value: 0.188595% CI: [-1, 5.2]Cochran-Mantel-Haenszel
Comparison: Analysis was stratified by region and baseline DMARD therapyp-value: 0.03395% CI: [0.3, 6.8]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With a Reduction in the HAQ-DI Score
Health Assessment Questionnaire - Disability Index (HAQ-DI): The Stanford Health Assessment Questionnaire disability index is a patient reported questionnaire specific for RA. It consists of 20 questions referring to eight component. Reduction in the HAQ-DI score of 0.25 units from baseline to weeks 24 and 48 represented a minimal clinically relevant improvement.
Time frame: Weeks 24 and 48
Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo x 2 IV + Non-Biologic DMARD | Percentage of Participants With a Reduction in the HAQ-DI Score | Percentage of Participants at Week 24 | 32.9 Percentage |
| Placebo x 2 IV + Non-Biologic DMARD | Percentage of Participants With a Reduction in the HAQ-DI Score | Percentage of Participants at Week 48 | 23.1 Percentage |
| Ocrelizumab 200 mg x 2 + Non-Biologic DMARD | Percentage of Participants With a Reduction in the HAQ-DI Score | Percentage of Participants at Week 24 | 52.3 Percentage |
| Ocrelizumab 200 mg x 2 + Non-Biologic DMARD | Percentage of Participants With a Reduction in the HAQ-DI Score | Percentage of Participants at Week 48 | 50.5 Percentage |
| Ocrelizumab 500 mg x 2 + Non-Biologic DMARD | Percentage of Participants With a Reduction in the HAQ-DI Score | Percentage of Participants at Week 24 | 58.5 Percentage |
| Ocrelizumab 500 mg x 2 + Non-Biologic DMARD | Percentage of Participants With a Reduction in the HAQ-DI Score | Percentage of Participants at Week 48 | 51.8 Percentage |
Comparison: At Week 24, analysis was stratified by region and baseline DMARD therapyp-value: <0.000195% CI: [11.3, 27.5]Cochran-Mantel-Haenszel
Comparison: At Week 24, analysis was stratified by region and baseline DMARD therapyp-value: <0.000195% CI: [16.8, 32.7]Cochran-Mantel-Haenszel
Comparison: At Week 48, analysis was stratified by region and baseline DMARD therapyp-value: <0.000195% CI: [19.5, 34.9]Cochran-Mantel-Haenszel
Comparison: At Week 48, analysis was stratified by region and baseline DMARD therapyp-value: <0.000195% CI: [20, 35.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With EULAR Response Rates of Good/ Moderate
The EULAR response rate was based on the assessment of disease activity using the DAS28. The EULAR response criteria included not only change in disease activity but current disease activity. To be classified as responders, participants had to have a significant change in DAS28 and a low current disease activity. There were 4 categories of EULAR response rates: good, moderate, good/moderate, and none.
Time frame: Weeks 24 and 48
Population: Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo x 2 IV + Non-Biologic DMARD | Percentage of Participants With EULAR Response Rates of Good/ Moderate | Week 48 | 24.9 Percentage |
| Placebo x 2 IV + Non-Biologic DMARD | Percentage of Participants With EULAR Response Rates of Good/ Moderate | Week 24 | 31.4 Percentage |
| Ocrelizumab 200 mg x 2 + Non-Biologic DMARD | Percentage of Participants With EULAR Response Rates of Good/ Moderate | Week 48 | 58.8 Percentage |
| Ocrelizumab 200 mg x 2 + Non-Biologic DMARD | Percentage of Participants With EULAR Response Rates of Good/ Moderate | Week 24 | 54.2 Percentage |
| Ocrelizumab 500 mg x 2 + Non-Biologic DMARD | Percentage of Participants With EULAR Response Rates of Good/ Moderate | Week 48 | 60.3 Percentage |
| Ocrelizumab 500 mg x 2 + Non-Biologic DMARD | Percentage of Participants With EULAR Response Rates of Good/ Moderate | Week 24 | 61.0 Percentage |
Comparison: At Week 24, analysis was stratified by region and baseline DMARD therapyp-value: <0.000195% CI: [1.85, 3.66]Proportional Odds Analysis
Comparison: At Week 24, analysis was stratified by region and baseline DMARD therapyp-value: <0.000195% CI: [2.49, 4.91]Proportional Odds Analysis
Comparison: At Week 48, analysis was stratified by region and baseline DMARD therapyp-value: <0.000195% CI: [2.93, 5.96]Proportional Odds Analysis
Comparison: At Week 48, analysis was stratified by region and baseline DMARD therapyp-value: <0.000195% CI: [3.54, 7.18]Proportional Odds Analysis