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| ID | Type | Description | Link |
|---|---|---|---|
| WA17047 |
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| Name | Class |
|---|---|
| Hoffmann-La Roche | INDUSTRY |
This is a phase III, randomized, controlled, double-blind, parallel group, international study in approximately 750 patients with active Rheumatoid Arthritis (RA) who are naive to Methotrexate (MTX) therapy. Rheumatoid Factor (RF)-positive and RF-negative patients will be enrolled and will be allocated equally between 3 treatment arms.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rituximab (0.5 g x 2) + Methotrexate | Experimental | 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 | Experimental | 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 |
|
| Placebo + Methotrexate | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| folate | Drug | Intravenous repeating dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Modified Total Sharp Score (mTSS) From Screening at Week 52 | 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. | Baseline and week 52 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Modified Sharp Erosion Score at 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. | Baseline and week 52 |
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Inclusion criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Arndt Schottelius, M.D. | Genentech, Inc. | Study Director |
Not provided
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22012969 | Derived | Tak PP, Rigby W, Rubbert-Roth A, Peterfy C, van Vollenhoven RF, Stohl W, Healy E, Hessey E, Reynard M, Shaw T. Sustained inhibition of progressive joint damage with rituximab plus methotrexate in early active rheumatoid arthritis: 2-year results from the randomised controlled trial IMAGE. Ann Rheum Dis. 2012 Mar;71(3):351-7. doi: 10.1136/annrheumdis-2011-200170. Epub 2011 Oct 19. | |
| 21557525 |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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 |
| FG002 | 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 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period |
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| Safety Follow-Up (SFU) Period |
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| Extended Safety Follow-Up (ESFU) Period |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Intent-to-treat population |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Modified Total Sharp Score (mTSS) From Screening at Week 52 | 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. | 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. | Posted | Mean | Standard Deviation | Score on a scale | Baseline and week 52 |
|
From Baseline to End of ESFU
Safety Population includes all participants who received at least one dose of study drug, grouped as treated. After Week 104 participants in the placebo group were eligible to receive either Rituximab 2 X 0.5 g + MTX or Rituximab 2 X 1.0g + MTX. Adverse events reported for placebo patients after switching to Rituximab are not included below.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infusion Related Reaction | Injury, poisoning and procedural complications | MedDRA 16.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Genentech, Inc. | 800-821-8590 | genentech@druginfo.com |
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D005492 | Folic Acid |
| D008727 | Methotrexate |
| D008775 | Methylprednisolone |
| D000069283 | Rituximab |
| ID | Term |
|---|---|
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
Not provided
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| methotrexate | Drug | Oral or parenteral repeating dose |
|
| methylprednisolone | Drug | Intravenous repeating dose |
|
| placebo | Drug | Intravenous repeating dose |
|
| rituximab | Drug | Intravenous repeating dose |
|
| Percentage of Patients Without Radiographic Progression at Week 52 | 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. | Baseline, Week 52 |
| Percentage of Patients Without Radiographic Progression in Total Erosion Score at 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. | Baseline, Week 52 |
| Change From Baseline in Modified Joint Space Narrowing (JSN) Score at 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. | Baseline and week 52 |
| Change From Baseline in the Modified Total Sharp Score at Week 24 | 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. | Baseline, Week 24 |
| Change From Baseline in the Total Erosion Score at Week 24 | 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. | Baseline, Week 24 |
| Change From Baseline in Modified Joint Space Narrowing (JSN) Score at 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. | Baseline, Week 24 |
| Percentage of Participants Without Radiographic Progression at Week 24 | 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. | Baseline, Week 24 |
| Percentage of Participants With American College of Rheumatology (ACR) ACR50 Response at Week 52 | 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:
| Week 52 |
| Change From Baseline in the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 52 | 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). | Baseline, Week 52 |
| Percentage of Participants With American College of Rheumatology (ACR) ACR70 Response at 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:
| Baseline, Week 52 |
| Percentage of Participants With DAS28-ESR Remission at Week 52 | 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 | Week 52 |
| Percentage of Participants With European League Against Rheumatism (EULAR) Good Response at Week 52 | 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. | Baseline, Week 52 |
| The Percentage of Participants With Major Clinical Response at Week 52 | 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:
| Week 52 |
| Percentage of Participants With DAS28-ESR Low Disease Activity at Week 52 | 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 | Week 52 |
| Percentage of Participants With American College of Rheumatology (ACR) ACR20 Response at 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:
| Baseline, Week 52 |
| Percentage of Participants With American College of Rheumatology (ACR) ACR90 Response at 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:
| Baseline, Week 52 |
| Change in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Score From Baseline at Week 52 | 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. | Baseline, Week 52 |
| Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52 | 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. | Baseline, Week 52 |
| Change From Baseline in the SF-36 Physical Health Component Summary Score at Week 52 and Week 104 | 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. | Baseline, Week 52, Week 104 |
| Change From Baseline in the SF-36 Mental Health Component Summary Score at Week 52 and Week 104 | 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. | Baseline, Weeks 52, Week 104 |
| Percentage of Participants With Categorical Change in Health Assessment Questionnaire- Disability Index (HAQ-DI) From Baseline at Week 52 | 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 | Baseline, Week 52 |
| Percentage of Patients With Minimally Clinically Important Difference (MCID) in the SF-36 Physical Health Component Score at Week 52 | 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. | Baseline, Week 52 |
| Percentage of Patients With Minimally Clinically Important Difference (MCID) in the SF-36 Mental Health Component Score at 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. | Baseline, Week 52 |
| Change From Baseline in the Modified Total Sharp Score at Week 104 | 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. | Baseline, Week 104 |
| Change From Baseline in the Total Erosion Score at 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 change from the score at baseline to week 104 is calculated. | Baseline, Week 104 |
| Percentage of Participants Without Radiographic Progression at 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. | Baseline, Week 104 |
| Percentage of Participants Without Radiographic Progression in the Total Erosion Score at 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. | Week 104 |
| Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 104 | 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. | Baseline, Week 104 |
| Derived |
| Rigby W, Ferraccioli G, Greenwald M, Zazueta-Montiel B, Fleischmann R, Wassenberg S, Ogale S, Armstrong G, Jahreis A, Burke L, Mela C, Chen A. Effect of rituximab on physical function and quality of life in patients with rheumatoid arthritis previously untreated with methotrexate. Arthritis Care Res (Hoboken). 2011 May;63(5):711-20. doi: 10.1002/acr.20419. |
| 20937671 | Derived | Tak PP, Rigby WF, Rubbert-Roth A, Peterfy CG, van Vollenhoven RF, Stohl W, Hessey E, Chen A, Tyrrell H, Shaw TM; IMAGE Investigators. Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial. Ann Rheum Dis. 2011 Jan;70(1):39-46. doi: 10.1136/ard.2010.137703. Epub 2010 Oct 11. |
| Insufficient therapeutic response |
|
| Failure to return |
|
| Violation of selection criteria |
|
| Protocol Violation |
|
| Refused treatment |
|
| Withdrew consent |
|
| Administrative reasons |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| BG001 |
| 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 |
| BG002 | 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 |
| BG003 | Total | Total of all reporting groups |
| Mean |
| Standard Deviation |
| years |
|
| Sex: Female, Male | Intent-to-treat population | Count of Participants | 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. |
| OG001 | 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 |
| OG002 | 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 |
|
|
|
| Secondary | Change From Baseline in Modified Sharp Erosion Score at 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. | 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. | Posted | Mean | Standard Deviation | Score on a scale | Baseline and week 52 |
|
|
|
|
| Secondary | Percentage of Patients Without Radiographic Progression at Week 52 | 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. | 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. | Posted | Number | Percentage | Baseline, Week 52 |
|
|
|
|
| Secondary | Percentage of Patients Without Radiographic Progression in Total Erosion Score at 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. | 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. | Posted | Number | Percentage of Participants | Baseline, Week 52 |
|
|
|
|
| Secondary | Change From Baseline in Modified Joint Space Narrowing (JSN) Score at 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. | 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. | Posted | Mean | Standard Deviation | Score on a scale | Baseline and week 52 |
|
|
|
|
| Secondary | Change From Baseline in the Modified Total Sharp Score at Week 24 | 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. | 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. | Posted | Mean | Standard Deviation | Score on a scale | Baseline, Week 24 |
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| Secondary | Change From Baseline in the Total Erosion Score at Week 24 | 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. | 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. | Posted | Mean | Standard Deviation | Score on a scale | Baseline, Week 24 |
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| Secondary | Change From Baseline in Modified Joint Space Narrowing (JSN) Score at 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. | Participants from the modified intent-to-treat population (includes patients with a screening and at least one post-baseline radiographic evaluation, grouped as randomized) with data available at Week 24 for analysis. | Posted | Mean | Standard Deviation | Score on a scale | Baseline, Week 24 |
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| Secondary | Percentage of Participants Without Radiographic Progression at Week 24 | 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. | 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 | Posted | Number | Percentage of Participants | Baseline, Week 24 |
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| Secondary | Percentage of Participants With American College of Rheumatology (ACR) ACR50 Response at Week 52 | 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:
| 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). | Posted | Number | Percentage of Participants | Week 52 |
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| Secondary | Change From Baseline in the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 52 | 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). | 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. | Posted | Mean | Standard Deviation | Score on a scale | Baseline, Week 52 |
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| Secondary | Percentage of Participants With American College of Rheumatology (ACR) ACR70 Response at 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:
| 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). | Posted | Number | Percentage of Participants | Baseline, Week 52 |
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| Secondary | Percentage of Participants With DAS28-ESR Remission at Week 52 | 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 | Participants from the Intent to treat (ITT) population includes all randomized participants who received at least one infusion with data available for analyses. | Posted | Number | Percentage of Participants | Week 52 |
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| Secondary | Percentage of Participants With European League Against Rheumatism (EULAR) Good Response at Week 52 | 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. | Intent to treat (ITT) population includes all randomized participants who received at least one infusion. Patients are considered non-responders if data are missing | Posted | Number | Percentage of Participants | Baseline, Week 52 |
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| Secondary | The Percentage of Participants With Major Clinical Response at Week 52 | 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:
| Intent to treat (ITT) population includes all randomized participants who received at least one infusion. | Posted | Number | Percentage of Participants | Week 52 |
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| Secondary | Percentage of Participants With DAS28-ESR Low Disease Activity at Week 52 | 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 | Participants from the Intent to treat (ITT) population includes all randomized participants who received at least one infusion who had data available for analyses. | Posted | Number | Percentage of Participants | Week 52 |
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| Secondary | Percentage of Participants With American College of Rheumatology (ACR) ACR20 Response at 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:
| 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). | Posted | Number | Percentage of Participants | Baseline, Week 52 |
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| Secondary | Percentage of Participants With American College of Rheumatology (ACR) ACR90 Response at 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:
| 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). | Posted | Number | Percentage of Participants | Baseline, Week 52 |
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| Secondary | Change in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Score From Baseline at Week 52 | 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. | 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. | Posted | Mean | Standard Deviation | Score on a scale | Baseline, Week 52 |
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| Secondary | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52 | 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. | Intent-to treat Population includes all randomized participants who received at least one dose of study drug. Last observation carried forward. | Posted | Mean | Standard Deviation | Score on a scale | Baseline, Week 52 |
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| Secondary | Change From Baseline in the SF-36 Physical Health Component Summary Score at Week 52 and Week 104 | 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. | 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. | Posted | Mean | Standard Deviation | Score on a scale | Baseline, Week 52, Week 104 |
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| Secondary | Change From Baseline in the SF-36 Mental Health Component Summary Score at Week 52 and Week 104 | 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. | 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. | Posted | Mean | Standard Deviation | Score on a scale | Baseline, Weeks 52, Week 104 |
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| Secondary | Percentage of Participants With Categorical Change in Health Assessment Questionnaire- Disability Index (HAQ-DI) From Baseline at Week 52 | 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 | Intent to treat (ITT) population includes all randomized participants who received at least one infusion. Last observation carried forward. | Posted | Number | Percentage of participants | Baseline, Week 52 |
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| Secondary | Percentage of Patients With Minimally Clinically Important Difference (MCID) in the SF-36 Physical Health Component Score at Week 52 | 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. | 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. | Posted | Number | Percentage of Participants | Baseline, Week 52 |
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| Secondary | Percentage of Patients With Minimally Clinically Important Difference (MCID) in the SF-36 Mental Health Component Score at 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. | 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. | Posted | Number | Percentage of Participants | Baseline, Week 52 |
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| Secondary | Change From Baseline in the Modified Total Sharp Score at Week 104 | 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. | 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. Linear extrapolation was used for missing data. | Posted | Mean | Standard Deviation | Score on a scale | Baseline, Week 104 |
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| Secondary | Change From Baseline in the Total Erosion Score at 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 change from the score at baseline to week 104 is calculated. | 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. | Posted | Mean | Standard Deviation | Score on a scale | Baseline, Week 104 |
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| Secondary | Percentage of Participants Without Radiographic Progression at 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. | 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 | Posted | Number | Percentage of Participants | Baseline, Week 104 |
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| Secondary | Percentage of Participants Without Radiographic Progression in the Total Erosion Score at 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. | 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. Patients with missing data are classified as progressing. | Posted | Number | Percentage of Participants | Week 104 |
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| Secondary | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 104 | 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. | 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. | Posted | Mean | Standard Deviation | Score on a scale | Baseline, Week 104 |
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| 48 |
| 249 |
| 193 |
| 249 |
| EG001 | 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 | 54 | 348 | 232 | 348 |
| EG002 | 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 | 58 | 263 | 208 | 263 |
| Urinary Tract Infection | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Appendicitis | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Acute Tonsillitis | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Febrile Infection | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Infection | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Lung Infection | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Pneumocystis Jirovecii Pneumonia | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Pneumonia Pneumococcal | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Septic Shock | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Subcutaneous Abscess | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Tonsillitis | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Inguinal Hernia | Gastrointestinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Appendicitis Perforated | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Diverticular Perforation | Gastrointestinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Gastrointestinal Haemorrhage | Gastrointestinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Gastrointestinal Hypomotility | Gastrointestinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Inguinal Hernia, Obstructive | Gastrointestinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Carotid Arteriosclerosis | Nervous system disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Embolic Stroke | Nervous system disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Epilepsy | Nervous system disorders | MedDRA 16.0 | Non-systematic Assessment |
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| Migraine | Nervous system disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Sciatica | Nervous system disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Transient Ischaemic Attack | Nervous system disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Carcinoma In Situ of Skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Non-systematic Assessment |
|
| Cervix Carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Non-systematic Assessment |
|
| Myelodysplastic Syndrome | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Non-systematic Assessment |
|
| Primary Mediastinal Large B-Cell Lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Non-systematic Assessment |
|
| Infusion Related Reaction | Injury, poisoning and procedural complications | MedDRA 16.0 | Non-systematic Assessment |
|
| Non-Cardiac Chest Pain | General disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Surgical Failure | General disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Myocardial Infarction | Cardiac disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Angina Pectoris | Cardiac disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Angina Unstable | Cardiac disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Atrioventricular Block Complete | Cardiac disorders | MedDRA 16.0 | Non-systematic Assessment |
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| Angiopathy | Vascular disorders | MedDRA 16.0 | Non-systematic Assessment |
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| Deep Vein Thrombosis | Vascular disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Hypertensive Crisis | Vascular disorders | MedDRA 16.0 | Non-systematic Assessment |
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| Pelvic Venous Thrombosis | Vascular disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Venous Insufficiency | Vascular disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA 16.0 | Non-systematic Assessment |
|
| Accident | Injury, poisoning and procedural complications | MedDRA 16.0 | Non-systematic Assessment |
|
| Femur Fracture | Injury, poisoning and procedural complications | MedDRA 16.0 | Non-systematic Assessment |
|
| Rheumatoid Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Cholecystitis | Hepatobiliary disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Cholelithiasis | Hepatobiliary disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Calculus Urinary | Renal and urinary disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Nephrolithiasis | Renal and urinary disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Vertigo Positional | Ear and labyrinth disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Diabetic Ketoacidosis | Metabolism and nutrition disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Cystocele | Reproductive system and breast disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Peritonitis | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Metastatic Malignant Melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Non-systematic Assessment |
|
| Interstitial Lung Disease | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Non-systematic Assessment |
|
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Status Asthmaticus | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Chest Pain | General disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Diverticulitis | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Endophthalmitis | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Gangrene | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Pulmonary Tuberculosis | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Pyelonephritis | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Abdominal Hernia | Gastrointestinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Colitis | Gastrointestinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Duodenal Ulcer | Gastrointestinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Gastrooesophageal Reflux Disease | Gastrointestinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Rectal Polyp | Gastrointestinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Umbilical Hernia | Gastrointestinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Breast Cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Non-systematic Assessment |
|
| Uterine Leiomyoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Non-systematic Assessment |
|
| Lung Neoplasm Malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Non-systematic Assessment |
|
| Prostate Cancer Stage II | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Non-systematic Assessment |
|
| Osteonecrosis | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Foot Deformity | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Pathological Fracture | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 16.0 | Non-systematic Assessment |
|
| Intentional Overdose | Injury, poisoning and procedural complications | MedDRA 16.0 | Non-systematic Assessment |
|
| Road Traffic Accident | Injury, poisoning and procedural complications | MedDRA 16.0 | Non-systematic Assessment |
|
| Cerebrovascular Accident | Nervous system disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Hypertensive Encephalopathy | Nervous system disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Laryngeal Hypertrophy | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Nasal Polyps | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Pulmonary Fibrosis | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Atrial Fibrillation | Cardiac disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Ulcer Haemorrhage | General disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Peripheral Ischaemia | Vascular disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Peripheral Vascular Disorder | Vascular disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Cholecystitis Acute | Hepatobiliary disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Cholangitis | Hepatobiliary disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Liver Disorder | Hepatobiliary disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Drug Dependence | Psychiatric disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Cervical Dysplasia | Reproductive system and breast disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Meniere's Disease | Ear and labyrinth disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Goitre | Endocrine disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Diabetes Mellitus | Metabolism and nutrition disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Abortion Induced | Surgical and medical procedures | MedDRA 16.0 | Non-systematic Assessment |
|
| Pyelonephritis Acute | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| Dengue Fever | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Abscess Limb | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| Arthritis Bacterial | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| Atypical Pneumonia | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| Colonic Abscess | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| H1N1 Influenza | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| Lower Respiratory Tract Infection | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| Necrotising Fasciitis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| Tracheobronchitis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| Endometrial Adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Systematic Assessment |
|
| Adenocarcinoma of Colon | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Non-systematic Assessment |
|
| Anaplastic Large-Cell Lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Non-systematic Assessment |
|
| Invasive Ductal Breast Carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Systematic Assessment |
|
| Lung Adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Non-systematic Assessment |
|
| Metastatic Neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Non-systematic Assessment |
|
| Monoclonal Gammopathy | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Systematic Assessment |
|
| Paget's Disease of Nipple | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Systematic Assessment |
|
| Colitis Ulcerative | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Intestinal Perforation | Gastrointestinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Large Intestinal Stenosis | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Ligament Sprain | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
|
| Multiple Fractures | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
|
| Rib Fracture | Injury, poisoning and procedural complications | MedDRA 16.0 | Non-systematic Assessment |
|
| Spinal Pain | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Acute Myocardial Infarction | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
|
| Coronary Artery Occlusion | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
|
| Mitral Valve Sclerosis | Cardiac disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Pericardial Effusion | Cardiac disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Supraventricular Tachycardia | Cardiac disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Respiratory Failure | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Cereberal Infarction | Nervous system disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Menorrhagia | Reproductive system and breast disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Ovarian Cyst Ruptured | Reproductive system and breast disorders | MedDRA 16.0 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Pancytopenia | Blood and lymphatic system disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Abortion Spontaneous | Pregnancy, puerperium and perinatal conditions | MedDRA 16.0 | Systematic Assessment |
|
| Diabetic Ulcer | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Respiratory Tract Infection | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| Gastrointestinal Dysplasia | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Upper Gastrointestinal Haemorrhage | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Intervertebral Disc Protrusion | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| Cerebral Infarction | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Rheumatoid Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA 16.0 | Non-systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 16.0 | Non-systematic Assessment |
|
| Drug-Induced Liver Injury | Hepatobiliary disorders | MedDRA 16.0 | Non-systematic Assessment |
|
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.
| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D006571 | Heterocyclic Compounds |
| D000630 | Aminopterin |
| D011239 | Prednisolone |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Rituximab 2 x 0.5 g + Methotrexate versus Placebo + Methotrexate, stratified for region and baseline RF status
| Van-Elteren |
| 0.1194 |
The Closure Principle was used to adjust for multiple comparisons. This was a secondary endpoint in a hierarchical testing structure. |
| 95 |
| Superiority or Other |
| Rituximab 2 x 1.0 g + Methotrexate versus Placebo + Methotrexate, stratified for region and baseline RF status | Van-Elteren | 0.0001 | The Closure Principle was used to adjust for multiple comparisons. This was a secondary endpoint in a hierarchical testing structure. | 95 | Superiority or Other |
Rituximab 2 x 1.0 g + Methotrexate arm versus Placebo + Methotrexate, stratified for region and baseline RF status |
| Cochran-Mantel-Haenszel |
| 0.0309 |
This was a secondary endpoint in a hierarchical testing structure. |
| Mean Difference (Net) |
| 0.10 |
| 95 |
| 0.01 |
| 0.18 |
| Superiority or Other |
Rituximab (1.0 g x 2) + Methotrexate verus Placebo + Methotrexate, stratified for region and Baseline RF status.
| Cochran-Mantel-Haenszel |
| 0.0081 |
This was a secondary endpoint in a hierarchical testing structure. |
| 95 |
| Superiority or Other |
Rituximab 2 x 0.5 g + Methotrexate arm versus Placebo + Methotrexate, stratified for region and baseline RF status
| Van-Elteren |
| 0.5478 |
The Closure Principle was used to adjust for multiple comparisons. This was a secondary endpoint in a hierarchical testing structure. |
| 95 |
| Superiority or Other |
| Rituximab 2 x 1.0 g + Methotrexate arm versus Placebo + Methotrexate, stratified for region and baseline RF status | Van-Elteren | 0.3096 | The Closure Principle was used to adjust for multiple comparisons. This was a secondary endpoint in a hierarchical testing structure. | 95 | Superiority or Other |
Rituximab 2 x 1.0 g + Methotrexate arm versus Placebo + Methotrexate, stratified for region and baseline RF status
| Cochran-Mantel-Haenszel |
| <0.0001 |
This was a secondary endpoint in a hierarchical testing structure. |
| 95 |
| Superiority or Other |
| ANOVA |
| <0.0001 |
Secondary endpoint in hierarchical testing structure. |
| 95 |
| Superiority or Other |
| Week 104 (n=240,236,242) |
|
|
| Title | Measurements |
|---|---|
|
| Worsened |
|
| Not Assessable |
|
Rituximab (1.0 g x 2) + Methotrexate versus Placebo + Methotrexate, stratified for region and baseline RF status.
| ANOVA |
| <0.0001 |
Secondary endpoint in hierarchical testing structure. |
| 95 |
| Superiority or Other |