IMAGE: A Study to Evaluate Rituximab in Combination With Methotrexate in Methotrexate-Naive Patients With Active Rheumatoid Arthritis
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: 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 |
Drug: folate
Intravenous repeating dose
Drug: methotrexate
Oral or parenteral repeating dose
Drug: methylprednisolone
Intravenous repeating dose
Drug: rituximab
Intravenous repeating dose
|
Experimental: 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 |
Drug: folate
Intravenous repeating dose
Drug: methotrexate
Oral or parenteral repeating dose
Drug: methylprednisolone
Intravenous repeating dose
Drug: rituximab
Intravenous repeating dose
|
Placebo Comparator: 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. |
Drug: folate
Intravenous repeating dose
Drug: methotrexate
Oral or parenteral repeating dose
Drug: methylprednisolone
Intravenous repeating dose
Drug: placebo
Intravenous repeating dose
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Modified Total Sharp Score (mTSS) From Screening at Week 52 [Baseline and 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.
Secondary Outcome Measures
- Change From Baseline in Modified Sharp Erosion Score at Week 52 [Baseline and week 52]
Rate of progression in structural joint damage (PJD) by change in modified Sharp erosion score from screening to Week 52. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. A score of 0 would indicate no change and higher scores represent a worsening of joint erosions.
- Percentage of Patients Without Radiographic Progression at Week 52 [Baseline, 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.
- Percentage of Patients Without Radiographic Progression in Total Erosion Score at Week 52 [Baseline, Week 52]
No radiographic progression is defined as a change in the total erosion score at Week 52 of less than or equal to zero.
- Change From Baseline in Modified Joint Space Narrowing (JSN) Score at Week 52 [Baseline and week 52]
Rate of progression in structural joint damage (PJD) by change in modified joint space narrowing (JSN) from screening to Week 52. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change and higher scores represent a worsening of joint space narrowing.
- Change From Baseline in the Modified Total Sharp Score at Week 24 [Baseline, 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.
- Change From Baseline in the Total Erosion Score at Week 24 [Baseline, 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.
- Change From Baseline in Modified Joint Space Narrowing (JSN) Score at Week 24 [Baseline, Week 24]
Joint Space Narrowing is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change and higher scores represent a worsening of joint space narrowing.
- Percentage of Participants Without Radiographic Progression at Week 24 [Baseline, 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.
- Percentage of Participants With American College of Rheumatology (ACR) ACR50 Response at Week 52 [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: the physician's global assessment of disease activity patient's global assessment of disease activity patient's assessment of pain HAQ-DI (Health Assessment Questionnaire disability index) an acute phase reactant C-Reactive Protein (CRP). (If CRP was missing then Erythrocyte Sedimentation Rate (ESR) was used if available.)
- Change From Baseline in the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 52 [Baseline, 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).
- Percentage of Participants With American College of Rheumatology (ACR) ACR70 Response at Week 52 [Baseline, Week 52]
To achieve an ACR70 response requires at least a 70% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 70% improvement in three of five additional measurements from: the physician's global assessment of disease activity patient's global assessment of disease activity patient's assessment of pain HAQ-DI (Health Assessment Questionnaire disability index) an acute phase reactant C-Reactive Protein (CRP). (If CRP was missing then Erythrocyte Sedimentation Rate (ESR) was used if available.)
- Percentage of Participants With DAS28-ESR Remission at Week 52 [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
- Percentage of Participants With European League Against Rheumatism (EULAR) Good Response at Week 52 [Baseline, 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.
- The Percentage of Participants With Major Clinical Response at Week 52 [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: the physician's global assessment of disease activity patient's global assessment of disease activity patient's assessment of pain HAQ-DI (Health Assessment Questionnaire disability index) an acute phase reactant C-Reactive Protein (CRP). (If CRP was missing then Erythrocyte Sedimentation Rate (ESR) was used if available.)
- Percentage of Participants With DAS28-ESR Low Disease Activity at Week 52 [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
- Percentage of Participants With American College of Rheumatology (ACR) ACR20 Response at Week 52 [Baseline, Week 52]
To achieve an ACR20 response requires at least a 20% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 20% improvement in three of five additional measurements from: the physician's global assessment of disease activity patient's global assessment of disease activity patient's assessment of pain HAQ-DI (Health Assessment Questionnaire disability index) an acute phase reactant C-Reactive Protein (CRP). (If CRP was missing then Erythrocyte Sedimentation Rate (ESR) was used if available.)
- Percentage of Participants With American College of Rheumatology (ACR) ACR90 Response at Week 52 [Baseline, Week 52]
To achieve an ACR90 response requires at least a 90% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 90% improvement in three of five additional measurements from: the physician's global assessment of disease activity patient's global assessment of disease activity patient's assessment of pain HAQ-DI (Health Assessment Questionnaire disability index) an acute phase reactant C-Reactive Protein (CRP). (If CRP was missing then Erythrocyte Sedimentation Rate (ESR) was used if available.)
- Change in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Score From Baseline at Week 52 [Baseline, 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.
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52 [Baseline, 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.
- Change From Baseline in the SF-36 Physical Health Component Summary Score at Week 52 and Week 104 [Baseline, Week 52, 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.
- Change From Baseline in the SF-36 Mental Health Component Summary Score at Week 52 and Week 104 [Baseline, Weeks 52, 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.
- Percentage of Participants With Categorical Change in Health Assessment Questionnaire- Disability Index (HAQ-DI) From Baseline at Week 52 [Baseline, 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
- Percentage of Patients With Minimally Clinically Important Difference (MCID) in the SF-36 Physical Health Component Score at Week 52 [Baseline, 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.
- Percentage of Patients With Minimally Clinically Important Difference (MCID) in the SF-36 Mental Health Component Score at Week 52 [Baseline, Week 52]
MCID is defined as a change from baseline in SF-36 Mental Health Component Score of >6.33. SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement.
- Change From Baseline in the Modified Total Sharp Score at Week 104 [Baseline, 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.
- Change From Baseline in the Total Erosion Score at Week 104 [Baseline, 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.
- Percentage of Participants Without Radiographic Progression at Week 104 [Baseline, Week 104]
Percentage of patients without radiographic progression at Week 104, defined as change in total modified Sharp score (TMSS) ≤ 0. TMSS is the sum of the erosion score (ES) and the joint space narrowing (JSN) score and has a range of 0 to 398. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change.
- Percentage of Participants Without Radiographic Progression in the Total Erosion Score at Week 104 [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.
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 104 [Baseline, 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.
Eligibility Criteria
Criteria
Inclusion criteria:
-
Adult patients 18-80 years of age
-
RA for ≥ 2 months;
-
Receiving outpatient treatment
-
Patients naive to, and considered to be candidates for, methotrexate treatment
Exclusion criteria:
-
Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA
-
Inflammatory joint disease other than RA, or other systemic autoimmune disorder
-
Diagnosis of juvenile rheumatoid arthritis, or RA before the age of 16
-
Surgery within 12 weeks of study
-
Previous treatment with any approved or investigational biologic agent for RA, an anti-alpha4-integrin antibody or co-stimulation modulator, or cell-depleting therapy
-
Concurrent treatment with any biologic agent or DMARD other than methotrexate
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Genentech, Inc.
- Hoffmann-La Roche
Investigators
- Study Director: Arndt Schottelius, M.D., Genentech, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- U3373g
- WA17047
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Period Title: Treatment Period | |||
STARTED | 251 | 252 | 252 |
Safety/ITT: Received Study Drug | 249 | 249 | 250 |
Completed Week 24 | 227 | 240 | 241 |
Completed Week 52 | 213 | 227 | 232 |
Completed Week 104 | 178 | 213 | 216 |
COMPLETED | 62 | 77 | 80 |
NOT COMPLETED | 189 | 175 | 172 |
Period Title: Treatment Period | |||
STARTED | 184 | 212 | 213 |
COMPLETED | 129 | 171 | 176 |
NOT COMPLETED | 55 | 41 | 37 |
Period Title: Treatment Period | |||
STARTED | 34 | 40 | 51 |
COMPLETED | 29 | 31 | 39 |
NOT COMPLETED | 5 | 9 | 12 |
Baseline Characteristics
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate | Total |
---|---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 intravenously at a dose of 1.0 g on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. Subsequent Rituximab treatment courses were given at 24 week intervals for 5 years provided the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS-ESR) result was ≥2.6 | Total of all reporting groups |
Overall Participants | 249 | 249 | 250 | 748 |
Age (years) [Mean (Standard Deviation) ] | ||||
Mean (Standard Deviation) [years] |
48.06
(12.692)
|
47.87
(13.391)
|
47.89
(13.324)
|
47.94
(13.136)
|
Sex: Female, Male (Count of Participants) | ||||
Female |
192
77.1%
|
203
81.5%
|
212
84.8%
|
607
81.1%
|
Male |
57
22.9%
|
46
18.5%
|
38
15.2%
|
141
18.9%
|
Outcome Measures
Title | Change From Baseline in Modified Total Sharp Score (mTSS) From Screening at Week 52 |
---|---|
Description | 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. |
Time Frame | Baseline and week 52 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 232 | 239 | 244 |
Mean (Standard Deviation) [Score on a scale] |
1.079
(4.0934)
|
0.646
(1.9196)
|
0.359
(1.0095)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo + Methotrexate, Rituximab (0.5 g x 2) + Methotrexate, Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|
Comments | Comparing all three treatment groups | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0016 |
Comments | The Closure Principle was used to adjust for multiple comparisons. | |
Method | Kruskal-Wallis | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo + Methotrexate, Rituximab (0.5 g x 2) + Methotrexate |
---|---|---|
Comments | Rituximab 2 x 0.5 g + Methotrexate arm versus Placebo + Methotrexate, stratified for region and baseline rheumatoid factor (RF) status | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.1824 |
Comments | The Closure Principle was used to adjust for multiple comparisons. | |
Method | Van-Elteren | |
Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Placebo + Methotrexate, Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|
Comments | Rituximab 2 x 1.0 g + Methotrexate arm versus Placebo + Methotrexate, stratified for region and baseline RF status | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0004 |
Comments | The Closure Principle was used to adjust for multiple comparisons. | |
Method | Van-Elteren | |
Comments |
Title | Change From Baseline in Modified Sharp Erosion Score at Week 52 |
---|---|
Description | 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. |
Time Frame | Baseline and week 52 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 232 | 239 | 244 |
Mean (Standard Deviation) [Score on a scale] |
0.738
(2.0480)
|
0.453
(1.2065)
|
0.233
(0.6252)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo + Methotrexate, Rituximab (0.5 g x 2) + Methotrexate, Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|
Comments | Comparing all three treatment groups | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0004 |
Comments | The Closure Principle was used to adjust for multiple comparisons. This was a secondary endpoint in a hierarchical testing structure. | |
Method | Kruskal-Wallis | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo + Methotrexate, Rituximab (0.5 g x 2) + Methotrexate |
---|---|---|
Comments | Rituximab 2 x 0.5 g + Methotrexate versus Placebo + Methotrexate, stratified for region and baseline RF status | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.1194 |
Comments | The Closure Principle was used to adjust for multiple comparisons. This was a secondary endpoint in a hierarchical testing structure. | |
Method | Van-Elteren | |
Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Placebo + Methotrexate, Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|
Comments | Rituximab 2 x 1.0 g + Methotrexate versus Placebo + Methotrexate, stratified for region and baseline RF status | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0001 |
Comments | The Closure Principle was used to adjust for multiple comparisons. This was a secondary endpoint in a hierarchical testing structure. | |
Method | Van-Elteren | |
Comments |
Title | Percentage of Patients Without Radiographic Progression at Week 52 |
---|---|
Description | 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. |
Time Frame | Baseline, Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 232 | 239 | 244 |
Number [Percentage] |
53.4
|
57.7
|
63.5
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo + Methotrexate, Rituximab (0.5 g x 2) + Methotrexate |
---|---|---|
Comments | Rituximab 2 x 0.5 g + Methotrexate arm versus Placebo + Methotrexate, stratified for region and baseline RF status | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.3803 |
Comments | This was a secondary endpoint in a hierarchical testing structure. | |
Method | Cochran-Mantel-Haenszel | |
Comments | ||
Method of Estimation | Estimation Parameter | Mean Difference (Net) |
Estimated Value | 0.04 | |
Confidence Interval |
() 95% -0.05 to 0.13 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo + Methotrexate, Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|
Comments | Rituximab 2 x 1.0 g + Methotrexate arm versus Placebo + Methotrexate, stratified for region and baseline RF status | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0309 |
Comments | This was a secondary endpoint in a hierarchical testing structure. | |
Method | Cochran-Mantel-Haenszel | |
Comments | ||
Method of Estimation | Estimation Parameter | Mean Difference (Net) |
Estimated Value | 0.10 | |
Confidence Interval |
() 95% 0.01 to 0.18 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Percentage of Patients Without Radiographic Progression in Total Erosion Score at Week 52 |
---|---|
Description | No radiographic progression is defined as a change in the total erosion score at Week 52 of less than or equal to zero. |
Time Frame | Baseline, Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 232 | 239 | 244 |
Number [Percentage of Participants] |
54.7
22%
|
59.0
23.7%
|
66.8
26.7%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo + Methotrexate, Rituximab (0.5 g x 2) + Methotrexate |
---|---|---|
Comments | Rituximab (0.5 g x 2) + Methotrexate versus Placebo + Methotrexate, stratified for region and baseline RF status. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.3752 |
Comments | This was a secondary endpoint in a hierarchical testing structure. | |
Method | Cochran-Mantel-Haenszel | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo + Methotrexate, Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|
Comments | Rituximab (1.0 g x 2) + Methotrexate verus Placebo + Methotrexate, stratified for region and Baseline RF status. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0081 |
Comments | This was a secondary endpoint in a hierarchical testing structure. | |
Method | Cochran-Mantel-Haenszel | |
Comments |
Title | Change From Baseline in Modified Joint Space Narrowing (JSN) Score at Week 52 |
---|---|
Description | 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. |
Time Frame | Baseline and week 52 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 232 | 239 | 244 |
Mean (Standard Deviation) [Score on a scale] |
0.341
(2.2408)
|
0.193
(0.9422)
|
0.126
(0.6363)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo + Methotrexate, Rituximab (0.5 g x 2) + Methotrexate, Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|
Comments | Comparing all three treatment groups. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.5939 |
Comments | The Closure Principle was used to adjust for multiple comparisons. This was a secondary endpoint in a hierarchical testing structure. | |
Method | Kruskal-Wallis | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo + Methotrexate, Rituximab (0.5 g x 2) + Methotrexate |
---|---|---|
Comments | Rituximab 2 x 0.5 g + Methotrexate arm versus Placebo + Methotrexate, stratified for region and baseline RF status | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.5478 |
Comments | The Closure Principle was used to adjust for multiple comparisons. This was a secondary endpoint in a hierarchical testing structure. | |
Method | Van-Elteren | |
Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Placebo + Methotrexate, Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|
Comments | Rituximab 2 x 1.0 g + Methotrexate arm versus Placebo + Methotrexate, stratified for region and baseline RF status | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.3096 |
Comments | The Closure Principle was used to adjust for multiple comparisons. This was a secondary endpoint in a hierarchical testing structure. | |
Method | Van-Elteren | |
Comments |
Title | Change From Baseline in the Modified Total Sharp Score at Week 24 |
---|---|
Description | 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. |
Time Frame | Baseline, Week 24 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 226 | 238 | 242 |
Mean (Standard Deviation) [Score on a scale] |
0.701
(2.9116)
|
0.508
(1.7349)
|
0.328
(0.9443)
|
Title | Change From Baseline in the Total Erosion Score at Week 24 |
---|---|
Description | 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. |
Time Frame | Baseline, Week 24 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 226 | 238 | 242 |
Mean (Standard Deviation) [Score on a scale] |
0.491
(1.3789)
|
0.404
(1.0390)
|
0.220
(0.5802)
|
Title | Change From Baseline in Modified Joint Space Narrowing (JSN) Score at Week 24 |
---|---|
Description | 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. |
Time Frame | Baseline, Week 24 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 226 | 238 | 242 |
Mean (Standard Deviation) [Score on a scale] |
0.210
(1.7403)
|
0.176
(0.8949)
|
0.108
(0.6118)
|
Title | Percentage of Participants Without Radiographic Progression at Week 24 |
---|---|
Description | 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. |
Time Frame | Baseline, Week 24 |
Outcome Measure Data
Analysis Population Description |
---|
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 |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 233 | 239 | 244 |
Number [Percentage of Participants] |
59.7
24%
|
65.3
26.2%
|
71.7
28.7%
|
Title | Percentage of Participants With American College of Rheumatology (ACR) ACR50 Response at Week 52 |
---|---|
Description | To achieve an ACR50 response requires at least a 50% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 50% improvement in three of five additional measurements from: the physician's global assessment of disease activity patient's global assessment of disease activity patient's assessment of pain HAQ-DI (Health Assessment Questionnaire disability index) an acute phase reactant C-Reactive Protein (CRP). (If CRP was missing then Erythrocyte Sedimentation Rate (ESR) was used if available.) |
Time Frame | Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
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). |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 249 | 249 | 250 |
Number [Percentage of Participants] |
41.8
16.8%
|
59.4
23.9%
|
64.8
25.9%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo + Methotrexate, Rituximab (0.5 g x 2) + Methotrexate |
---|---|---|
Comments | Rituximab 2 x 0.5 g + Methotrexate arm versus Placebo + Methotrexate, stratified for region and baseline RF status | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | This was a secondary endpoint in a hierarchical testing structure. | |
Method | Cochran-Mantel-Haenszel | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo + Methotrexate, Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|
Comments | Rituximab 2 x 1.0 g + Methotrexate arm versus Placebo + Methotrexate, stratified for region and baseline RF status | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | This was a secondary endpoint in a hierarchical testing structure. | |
Method | Cochran-Mantel-Haenszel | |
Comments |
Title | Change From Baseline in the Disease Activity Score 28 Joint Count- Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 52 |
---|---|
Description | 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). |
Time Frame | Baseline, Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 244 | 247 | 248 |
Mean (Standard Deviation) [Score on a scale] |
-2.33
(1.691)
|
-3.35
(1.663)
|
-3.46
(1.640)
|
Title | Percentage of Participants With American College of Rheumatology (ACR) ACR70 Response at Week 52 |
---|---|
Description | To achieve an ACR70 response requires at least a 70% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 70% improvement in three of five additional measurements from: the physician's global assessment of disease activity patient's global assessment of disease activity patient's assessment of pain HAQ-DI (Health Assessment Questionnaire disability index) an acute phase reactant C-Reactive Protein (CRP). (If CRP was missing then Erythrocyte Sedimentation Rate (ESR) was used if available.) |
Time Frame | Baseline, Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
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). |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 249 | 249 | 250 |
Number [Percentage of Participants] |
24.9
10%
|
42.2
16.9%
|
46.8
18.7%
|
Title | Percentage of Participants With DAS28-ESR Remission at Week 52 |
---|---|
Description | 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 |
Time Frame | Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
Participants from the Intent to treat (ITT) population includes all randomized participants who received at least one infusion with data available for analyses. |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 247 | 248 | 249 |
Number [Percentage of Participants] |
12.6
5.1%
|
25.4
10.2%
|
30.5
12.2%
|
Title | Percentage of Participants With European League Against Rheumatism (EULAR) Good Response at Week 52 |
---|---|
Description | 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. |
Time Frame | Baseline, Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
Intent to treat (ITT) population includes all randomized participants who received at least one infusion. Patients are considered non-responders if data are missing |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 249 | 249 | 250 |
Number [Percentage of Participants] |
18.1
7.3%
|
39.0
15.7%
|
41.6
16.6%
|
Title | The Percentage of Participants With Major Clinical Response at Week 52 |
---|---|
Description | Major clinical response is defined as a continuous six-month period of success by the ACR70. ACR70= 70% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 70% improvement in 3 of five additional measurements from: the physician's global assessment of disease activity patient's global assessment of disease activity patient's assessment of pain HAQ-DI (Health Assessment Questionnaire disability index) an acute phase reactant C-Reactive Protein (CRP). (If CRP was missing then Erythrocyte Sedimentation Rate (ESR) was used if available.) |
Time Frame | Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
Intent to treat (ITT) population includes all randomized participants who received at least one infusion. |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 249 | 249 | 250 |
Number [Percentage of Participants] |
8.4
3.4%
|
18.1
7.3%
|
21.2
8.5%
|
Title | Percentage of Participants With DAS28-ESR Low Disease Activity at Week 52 |
---|---|
Description | 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 |
Time Frame | Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
Participants from the Intent to treat (ITT) population includes all randomized participants who received at least one infusion who had data available for analyses. |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 247 | 248 | 249 |
Number [Percentage of Participants] |
19.8
8%
|
40.3
16.2%
|
43.0
17.2%
|
Title | Percentage of Participants With American College of Rheumatology (ACR) ACR20 Response at Week 52 |
---|---|
Description | To achieve an ACR20 response requires at least a 20% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 20% improvement in three of five additional measurements from: the physician's global assessment of disease activity patient's global assessment of disease activity patient's assessment of pain HAQ-DI (Health Assessment Questionnaire disability index) an acute phase reactant C-Reactive Protein (CRP). (If CRP was missing then Erythrocyte Sedimentation Rate (ESR) was used if available.) |
Time Frame | Baseline, Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
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). |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 249 | 249 | 250 |
Number [Percentage of Participants] |
64.3
25.8%
|
76.7
30.8%
|
80.0
32%
|
Title | Percentage of Participants With American College of Rheumatology (ACR) ACR90 Response at Week 52 |
---|---|
Description | To achieve an ACR90 response requires at least a 90% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 90% improvement in three of five additional measurements from: the physician's global assessment of disease activity patient's global assessment of disease activity patient's assessment of pain HAQ-DI (Health Assessment Questionnaire disability index) an acute phase reactant C-Reactive Protein (CRP). (If CRP was missing then Erythrocyte Sedimentation Rate (ESR) was used if available.) |
Time Frame | Baseline, Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
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). |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 249 | 249 | 250 |
Number [Percentage of Participants] |
9.2
3.7%
|
17.3
6.9%
|
16.4
6.6%
|
Title | Change in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Score From Baseline at Week 52 |
---|---|
Description | 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. |
Time Frame | Baseline, Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 198 | 206 | 218 |
Mean (Standard Deviation) [Score on a scale] |
10.154
(11.1344)
|
11.833
(11.5807)
|
12.426
(12.2535)
|
Title | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52 |
---|---|
Description | 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. |
Time Frame | Baseline, Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to treat Population includes all randomized participants who received at least one dose of study drug. Last observation carried forward. |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 248 | 247 | 249 |
Mean (Standard Deviation) [Score on a scale] |
-0.800
(0.7764)
|
-1.038
(0.7625)
|
-1.023
(0.7634)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo + Methotrexate, Rituximab (0.5 g x 2) + Methotrexate |
---|---|---|
Comments | Rituximab (0.5 g x 2) + Methotrexate versus Placebo + Methotrexate stratified for region and RF status. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | Secondary endpoint in hierarchical testing structure. | |
Method | ANOVA | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo + Methotrexate, Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|
Comments | Rituximab (1.0 g x 2) + Methotrexate versus Placebo + Methotrexate, stratified for region and baseline RF status. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | Secondary endpoint in hierarchical testing structure. | |
Method | ANOVA | |
Comments |
Title | Change From Baseline in the SF-36 Physical Health Component Summary Score at Week 52 and Week 104 |
---|---|
Description | 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. |
Time Frame | Baseline, Week 52, Week 104 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 249 | 249 | 250 |
Week 52 (n=239,236,241) |
8.953
(9.3986)
|
11.022
(9.6246)
|
12.205
(9.4986)
|
Week 104 (n=240,236,242) |
8.617
(9.8500)
|
11.032
(9.9631)
|
12.649
(10.4331)
|
Title | Change From Baseline in the SF-36 Mental Health Component Summary Score at Week 52 and Week 104 |
---|---|
Description | 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. |
Time Frame | Baseline, Weeks 52, Week 104 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 249 | 249 | 250 |
Week 52 (n=239,236,241) |
6.689
(13.1160)
|
7.718
(11.8903)
|
8.167
(12.1709)
|
Week 104 (n= 240,236,242) |
6.295
(13.9813)
|
7.617
(12.0793)
|
9.066
(12.5325)
|
Title | Percentage of Participants With Categorical Change in Health Assessment Questionnaire- Disability Index (HAQ-DI) From Baseline at Week 52 |
---|---|
Description | 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 |
Time Frame | Baseline, Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
Intent to treat (ITT) population includes all randomized participants who received at least one infusion. Last observation carried forward. |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 249 | 249 | 250 |
Improved |
77.1
31%
|
86.7
34.8%
|
86.8
34.7%
|
Unchanged |
14.1
5.7%
|
8.8
3.5%
|
8.0
3.2%
|
Worsened |
8.4
3.4%
|
3.6
1.4%
|
4.4
1.8%
|
Not Assessable |
0.4
0.2%
|
0.8
0.3%
|
0.8
0.3%
|
Title | Percentage of Patients With Minimally Clinically Important Difference (MCID) in the SF-36 Physical Health Component Score at Week 52 |
---|---|
Description | 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. |
Time Frame | Baseline, Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 239 | 236 | 242 |
Number [Percentage of Participants] |
63.2
25.4%
|
69.9
28.1%
|
76.4
30.6%
|
Title | Percentage of Patients With Minimally Clinically Important Difference (MCID) in the SF-36 Mental Health Component Score at Week 52 |
---|---|
Description | 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. |
Time Frame | Baseline, Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 239 | 236 | 242 |
Number [Percentage of Participants] |
49.0
19.7%
|
50.8
20.4%
|
57.0
22.8%
|
Title | Change From Baseline in the Modified Total Sharp Score at Week 104 |
---|---|
Description | 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. |
Time Frame | Baseline, Week 104 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 229 | 238 | 243 |
Mean (Standard Deviation) [Score on a scale] |
1.948
(5.5782)
|
0.761
(2.6181)
|
0.406
(1.4312)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo + Methotrexate, Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|
Comments | Week 104: Rituximab 2 x 0.5 g + Methotrexate arm versus Placebo + Methotrexate, stratified for region and baseline rheumatoid factor (RF) status. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | This was a secondary endpoint in a hierarchical testing structure. | |
Method | Van-Elteren | |
Comments |
Title | Change From Baseline in the Total Erosion Score at Week 104 |
---|---|
Description | 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. |
Time Frame | Baseline, Week 104 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 229 | 238 | 243 |
Mean (Standard Deviation) [Score on a scale] |
1.315
(3.2466)
|
0.499
(1.7221)
|
0.227
(0.7939)
|
Title | Percentage of Participants Without Radiographic Progression at Week 104 |
---|---|
Description | 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. |
Time Frame | Baseline, Week 104 |
Outcome Measure Data
Analysis Population Description |
---|
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 |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 233 | 239 | 244 |
Number [Percentage of Participants] |
37.3
15%
|
49.4
19.8%
|
56.6
22.6%
|
Title | Percentage of Participants Without Radiographic Progression in the Total Erosion Score at Week 104 |
---|---|
Description | 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. |
Time Frame | Week 104 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 233 | 239 | 244 |
Number [Percentage of Participants] |
38.2
15.3%
|
52.7
21.2%
|
58.6
23.4%
|
Title | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 104 |
---|---|
Description | 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. |
Time Frame | Baseline, Week 104 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|---|
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 |
Measure Participants | 248 | 247 | 248 |
Mean (Standard Deviation) [Score on a scale] |
-0.806
(0.7968)
|
-1038
(0.8142)
|
-1.055
(0.7901)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo + Methotrexate, Rituximab (0.5 g x 2) + Methotrexate |
---|---|---|
Comments | Rituximab (0.5 g x 2) + Methotrexate versus Placebo + Methotrexate, stratified for region and baseline RF status. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | Secondary endpoint in hierarchical testing structure. | |
Method | ANOVA | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo + Methotrexate, Rituximab (1.0 g x 2) + Methotrexate |
---|---|---|
Comments | Rituximab (1.0 g x 2) + Methotrexate versus Placebo + Methotrexate, stratified for region and baseline RF status. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | Secondary endpoint in hierarchical testing structure. | |
Method | ANOVA | |
Comments |
Adverse Events
Time Frame | From Baseline to End of ESFU | |||||
---|---|---|---|---|---|---|
Adverse Event Reporting Description | 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. | |||||
Arm/Group Title | Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate | |||
Arm/Group Description | Placebo intravenously on Days 1 and 15 + a background of methotrexate orally at a dose of 7.5 mg escalating by 2.5 mg a week every 1-2 weeks to achieve: 15 mg per week by Week 4 and 20 mg per week by Week 8. From Week 104 participants were eligible to receive Rituximab 2 X 0.5 g or Rituximab 2 X 1.0 g every 24 weeks. | Rituximab 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 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 | |||
All Cause Mortality |
||||||
Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 48/249 (19.3%) | 54/348 (15.5%) | 58/263 (22.1%) | |||
Blood and lymphatic system disorders | ||||||
Neutropenia | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Pancytopenia | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Cardiac disorders | ||||||
Myocardial Infarction | 0/249 (0%) | 2/348 (0.6%) | 1/263 (0.4%) | |||
Angina Pectoris | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Angina Unstable | 1/249 (0.4%) | 0/348 (0%) | 1/263 (0.4%) | |||
Atrioventricular Block Complete | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Atrial Fibrillation | 0/249 (0%) | 1/348 (0.3%) | 2/263 (0.8%) | |||
Acute Myocardial Infarction | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Coronary Artery Occlusion | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Mitral Valve Sclerosis | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Pericardial Effusion | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Supraventricular Tachycardia | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Ear and labyrinth disorders | ||||||
Vertigo Positional | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Meniere's Disease | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Endocrine disorders | ||||||
Goitre | 1/249 (0.4%) | 0/348 (0%) | 1/263 (0.4%) | |||
Gastrointestinal disorders | ||||||
Inguinal Hernia | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Diarrhoea | 1/249 (0.4%) | 0/348 (0%) | 1/263 (0.4%) | |||
Diverticular Perforation | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Gastrointestinal Haemorrhage | 1/249 (0.4%) | 0/348 (0%) | 1/263 (0.4%) | |||
Gastrointestinal Hypomotility | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Inguinal Hernia, Obstructive | 0/249 (0%) | 1/348 (0.3%) | 1/263 (0.4%) | |||
Abdominal Hernia | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Colitis | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Duodenal Ulcer | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Gastritis | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Gastrooesophageal Reflux Disease | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Rectal Polyp | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Umbilical Hernia | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Colitis Ulcerative | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Intestinal Perforation | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Large Intestinal Stenosis | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Gastrointestinal Dysplasia | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Upper Gastrointestinal Haemorrhage | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
General disorders | ||||||
Non-Cardiac Chest Pain | 1/249 (0.4%) | 0/348 (0%) | 1/263 (0.4%) | |||
Surgical Failure | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Chest Pain | 1/249 (0.4%) | 2/348 (0.6%) | 2/263 (0.8%) | |||
Ulcer Haemorrhage | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Hepatobiliary disorders | ||||||
Cholecystitis | 0/249 (0%) | 2/348 (0.6%) | 1/263 (0.4%) | |||
Cholelithiasis | 1/249 (0.4%) | 0/348 (0%) | 1/263 (0.4%) | |||
Cholecystitis Acute | 1/249 (0.4%) | 0/348 (0%) | 1/263 (0.4%) | |||
Cholangitis | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Liver Disorder | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Infections and infestations | ||||||
Pneumonia | 6/249 (2.4%) | 7/348 (2%) | 4/263 (1.5%) | |||
Urinary Tract Infection | 4/249 (1.6%) | 2/348 (0.6%) | 0/263 (0%) | |||
Appendicitis | 0/249 (0%) | 2/348 (0.6%) | 0/263 (0%) | |||
Acute Tonsillitis | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Cellulitis | 0/249 (0%) | 1/348 (0.3%) | 1/263 (0.4%) | |||
Febrile Infection | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Gastroenteritis | 0/249 (0%) | 1/348 (0.3%) | 1/263 (0.4%) | |||
Infection | 0/249 (0%) | 0/348 (0%) | 3/263 (1.1%) | |||
Lung Infection | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Pneumocystis Jirovecii Pneumonia | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Pneumonia Pneumococcal | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Septic Shock | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Subcutaneous Abscess | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Tonsillitis | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Appendicitis Perforated | 1/249 (0.4%) | 1/348 (0.3%) | 0/263 (0%) | |||
Peritonitis | 1/249 (0.4%) | 0/348 (0%) | 1/263 (0.4%) | |||
Diverticulitis | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Endophthalmitis | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Gangrene | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Pulmonary Tuberculosis | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Pyelonephritis | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Pyelonephritis Acute | 1/249 (0.4%) | 2/348 (0.6%) | 0/263 (0%) | |||
Dengue Fever | 0/249 (0%) | 1/348 (0.3%) | 1/263 (0.4%) | |||
Abscess Limb | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Arthritis Bacterial | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Atypical Pneumonia | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Colonic Abscess | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
H1N1 Influenza | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Influenza | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Lower Respiratory Tract Infection | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Necrotising Fasciitis | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Sepsis | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Tracheobronchitis | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Respiratory Tract Infection | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Bronchitis | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Injury, poisoning and procedural complications | ||||||
Infusion Related Reaction | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Fall | 3/249 (1.2%) | 2/348 (0.6%) | 1/263 (0.4%) | |||
Accident | 1/249 (0.4%) | 0/348 (0%) | 1/263 (0.4%) | |||
Femur Fracture | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Contusion | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Intentional Overdose | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Road Traffic Accident | 2/249 (0.8%) | 1/348 (0.3%) | 0/263 (0%) | |||
Ligament Sprain | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Multiple Fractures | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Rib Fracture | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Metabolism and nutrition disorders | ||||||
Diabetic Ketoacidosis | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Diabetes Mellitus | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Musculoskeletal and connective tissue disorders | ||||||
Rheumatoid Arthritis | 1/249 (0.4%) | 3/348 (0.9%) | 2/263 (0.8%) | |||
Bursitis | 1/249 (0.4%) | 1/348 (0.3%) | 0/263 (0%) | |||
Osteonecrosis | 1/249 (0.4%) | 0/348 (0%) | 1/263 (0.4%) | |||
Arthritis | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Foot Deformity | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Pathological Fracture | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Spinal Pain | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Intervertebral Disc Protrusion | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
Carcinoma In Situ of Skin | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Cervix Carcinoma | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Myelodysplastic Syndrome | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Primary Mediastinal Large B-Cell Lymphoma | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Metastatic Malignant Melanoma | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Lymphoma | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Breast Cancer | 0/249 (0%) | 1/348 (0.3%) | 1/263 (0.4%) | |||
Uterine Leiomyoma | 1/249 (0.4%) | 0/348 (0%) | 1/263 (0.4%) | |||
Lung Neoplasm Malignant | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Prostate Cancer Stage II | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Endometrial Adenocarcinoma | 1/249 (0.4%) | 1/348 (0.3%) | 0/263 (0%) | |||
Adenocarcinoma of Colon | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Anaplastic Large-Cell Lymphoma | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Invasive Ductal Breast Carcinoma | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Lung Adenocarcinoma | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Metastatic Neoplasm | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Monoclonal Gammopathy | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Paget's Disease of Nipple | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Nervous system disorders | ||||||
Carotid Arteriosclerosis | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Embolic Stroke | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Epilepsy | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Migraine | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Sciatica | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Syncope | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Transient Ischaemic Attack | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Cerebrovascular Accident | 0/249 (0%) | 1/348 (0.3%) | 1/263 (0.4%) | |||
Hypertensive Encephalopathy | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Cereberal Infarction | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Convulsion | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Cerebral Infarction | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Headache | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Pregnancy, puerperium and perinatal conditions | ||||||
Abortion Spontaneous | 0/249 (0%) | 1/348 (0.3%) | 1/263 (0.4%) | |||
Psychiatric disorders | ||||||
Anxiety | 0/249 (0%) | 0/348 (0%) | 2/263 (0.8%) | |||
Depression | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Drug Dependence | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Renal and urinary disorders | ||||||
Calculus Urinary | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Nephrolithiasis | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Reproductive system and breast disorders | ||||||
Cystocele | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Cervical Dysplasia | 2/249 (0.8%) | 0/348 (0%) | 0/263 (0%) | |||
Menorrhagia | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Ovarian Cyst Ruptured | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Respiratory, thoracic and mediastinal disorders | ||||||
Interstitial Lung Disease | 1/249 (0.4%) | 1/348 (0.3%) | 2/263 (0.8%) | |||
Dyspnoea | 0/249 (0%) | 1/348 (0.3%) | 1/263 (0.4%) | |||
Epistaxis | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Pulmonary Embolism | 1/249 (0.4%) | 1/348 (0.3%) | 0/263 (0%) | |||
Status Asthmaticus | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Laryngeal Hypertrophy | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Nasal Polyps | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Pulmonary Fibrosis | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Asthma | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Respiratory Failure | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Skin and subcutaneous tissue disorders | ||||||
Diabetic Ulcer | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Surgical and medical procedures | ||||||
Abortion Induced | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Vascular disorders | ||||||
Angiopathy | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Deep Vein Thrombosis | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Hypertensive Crisis | 0/249 (0%) | 0/348 (0%) | 1/263 (0.4%) | |||
Pelvic Venous Thrombosis | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Venous Insufficiency | 0/249 (0%) | 1/348 (0.3%) | 1/263 (0.4%) | |||
Hypertension | 1/249 (0.4%) | 0/348 (0%) | 0/263 (0%) | |||
Peripheral Ischaemia | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Peripheral Vascular Disorder | 0/249 (0%) | 1/348 (0.3%) | 0/263 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
Placebo + Methotrexate | Rituximab (0.5 g x 2) + Methotrexate | Rituximab (1.0 g x 2) + Methotrexate | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 193/249 (77.5%) | 232/348 (66.7%) | 208/263 (79.1%) | |||
Blood and lymphatic system disorders | ||||||
Anaemia | 25/249 (10%) | 14/348 (4%) | 19/263 (7.2%) | |||
Gastrointestinal disorders | ||||||
Nausea | 42/249 (16.9%) | 45/348 (12.9%) | 46/263 (17.5%) | |||
Diarrhoea | 15/249 (6%) | 24/348 (6.9%) | 18/263 (6.8%) | |||
Dyspepsia | 13/249 (5.2%) | 15/348 (4.3%) | 14/263 (5.3%) | |||
Gastritis | 13/249 (5.2%) | 11/348 (3.2%) | 10/263 (3.8%) | |||
Hepatobiliary disorders | ||||||
Drug-Induced Liver Injury | 35/249 (14.1%) | 37/348 (10.6%) | 38/263 (14.4%) | |||
Infections and infestations | ||||||
Upper Respiratory Tract Infection | 44/249 (17.7%) | 59/348 (17%) | 58/263 (22.1%) | |||
Nasopharyngitis | 43/249 (17.3%) | 53/348 (15.2%) | 52/263 (19.8%) | |||
Urinary Tract Infection | 26/249 (10.4%) | 36/348 (10.3%) | 43/263 (16.3%) | |||
Bronchitis | 15/249 (6%) | 32/348 (9.2%) | 20/263 (7.6%) | |||
Sinusitis | 11/249 (4.4%) | 23/348 (6.6%) | 20/263 (7.6%) | |||
Pharyngitis | 16/249 (6.4%) | 14/348 (4%) | 14/263 (5.3%) | |||
Gastroenteritis | 7/249 (2.8%) | 9/348 (2.6%) | 16/263 (6.1%) | |||
Influenza | 11/249 (4.4%) | 9/348 (2.6%) | 16/263 (6.1%) | |||
Injury, poisoning and procedural complications | ||||||
Infusion Related Reaction | 53/249 (21.3%) | 69/348 (19.8%) | 67/263 (25.5%) | |||
Musculoskeletal and connective tissue disorders | ||||||
Rheumatoid Arthritis | 42/249 (16.9%) | 30/348 (8.6%) | 29/263 (11%) | |||
Back pain | 14/249 (5.6%) | 19/348 (5.5%) | 9/263 (3.4%) | |||
Nervous system disorders | ||||||
Headache | 18/249 (7.2%) | 17/348 (4.9%) | 31/263 (11.8%) | |||
Dizziness | 13/249 (5.2%) | 12/348 (3.4%) | 20/263 (7.6%) | |||
Respiratory, thoracic and mediastinal disorders | ||||||
Cough | 11/249 (4.4%) | 19/348 (5.5%) | 24/263 (9.1%) | |||
Vascular disorders | ||||||
Hypertension | 18/249 (7.2%) | 22/348 (6.3%) | 24/263 (9.1%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
Name/Title | Medical Communications |
---|---|
Organization | Genentech, Inc. |
Phone | 800-821-8590 |
genentech@druginfo.com |
- U3373g
- WA17047