Back to resultsA Study to Evaluate Rituximab in Combination With Methotrexate in Methotrexate-Naive Patients With Active Rheumatoid Arthritis (IMAGE)
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
folate
methotrexate
methylprednisolone
placebo
rituximab
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rituxan, MTX, RA, IMAGE, WA17047
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Rituximab (0.5 g x 2) + Methotrexate
Rituximab (1.0 g x 2) + Methotrexate
Placebo + Methotrexate
Arm Description
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
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.
Outcomes
Primary Outcome Measures
Change From Baseline in Modified Total Sharp Score (mTSS) From Screening at Week 52
Rate of progression in structural joint damage (PJD) by change in Total Modified Sharp Score (TMSS) from screening to Week 52 in the modified intent-to-treat (MITT) population. TMSS is the sum of the erosion score (ES) and the joint space narrowing (JSN) score and has a range of 0 to 398. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change and higher scores represent a worsening of joint erosions and joint space narrowing.
Secondary Outcome Measures
Change From Baseline in Modified Sharp Erosion Score at Week 52
Rate of progression in structural joint damage (PJD) by change in modified Sharp erosion score from screening to Week 52. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. A score of 0 would indicate no change and higher scores represent a worsening of joint erosions.
Percentage of Patients Without Radiographic Progression at Week 52
Percentage of patients without radiographic progression at Week 52, defined as change in total modified Sharp score (TMSS) <= 0. TMSS is the sum of the erosion score (ES) and the joint space narrowing (JSN) score and has a range of 0 to 398. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change.
Percentage of Patients Without Radiographic Progression in Total Erosion Score at Week 52
No radiographic progression is defined as a change in the total erosion score at Week 52 of less than or equal to zero.
Change From Baseline in Modified Joint Space Narrowing (JSN) Score at Week 52
Rate of progression in structural joint damage (PJD) by change in modified joint space narrowing (JSN) from screening to Week 52. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change and higher scores represent a worsening of joint space narrowing.
Change From Baseline in the Modified Total Sharp Score at Week 24
The modified total sharp score is the sum of the erosion score (ES) and the joint space narrowing (JSN) score and has a range of 0 to 398. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change and higher scores represent a worsening of joint erosions and joint space narrowing.
Change From Baseline in the Total Erosion Score at Week 24
Total Erosion Score is determined by evaluation of fourteen sites in each wrist and hand and six joints in each foot using an eight-point scale from 0 (normal: no erosions) to 3.5 (Very severe; erosions of 100% of the articular surfaces. The Total Erosion Score at Week 24 - Total Erosion Score at baseline is calculated.
Change From Baseline in Modified Joint Space Narrowing (JSN) Score at Week 24
Joint Space Narrowing is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change and higher scores represent a worsening of joint space narrowing.
Percentage of Participants Without Radiographic Progression at Week 24
Percentage of patients without radiographic progression at Week 24 defined as change in total modified Sharp score (TMSS) ≤ 0. TMSS is the sum of the erosion score (ES) and the joint space narrowing (JSN) score and has a range of 0 to 398. The ES is the sum of joint scores collected for 46 joints and has a range of 0 to 230. The JSN is the sum of joint scores collected for 42 joints and has a range of 0 to 168. A score of 0 would indicate no change.
Percentage of Participants With American College of Rheumatology (ACR) ACR50 Response at Week 52
To achieve an ACR50 response requires at least a 50% improvement compared with baseline in both Total Joint Count and Swollen Joint Count, as well as a 50% improvement in three of five additional measurements from:
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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.
Full Information
NCT ID
NCT00299104
First Posted
March 2, 2006
Last Updated
June 29, 2017
Sponsor
Genentech, Inc.
Collaborators
Hoffmann-La Roche
1. Study Identification
Unique Protocol Identification Number
NCT00299104
Brief Title
A Study to Evaluate Rituximab in Combination With Methotrexate in Methotrexate-Naive Patients With Active Rheumatoid Arthritis
Acronym
IMAGE
Official Title
A Randomized, Phase 3, Controlled, Double-Blind, Parallel-Group, Multicenter Study to Evaluate the Safety and Efficacy of Rituximab in Combination With Methotrexate (MTX) Compared to MTX Alone, in Methotrexate-Naive Patients With Active Rheumatoid Arthritis
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
January 2006 (undefined)
Primary Completion Date
September 2008 (Actual)
Study Completion Date
July 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
Collaborators
Hoffmann-La Roche
4. Oversight
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rituxan, MTX, RA, IMAGE, WA17047
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
755 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rituximab (0.5 g x 2) + Methotrexate
Arm Type
Experimental
Arm Description
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
Arm Title
Rituximab (1.0 g x 2) + Methotrexate
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo + Methotrexate
Arm Type
Placebo Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
folate
Intervention Description
Intravenous repeating dose
Intervention Type
Drug
Intervention Name(s)
methotrexate
Intervention Description
Oral or parenteral repeating dose
Intervention Type
Drug
Intervention Name(s)
methylprednisolone
Intervention Description
Intravenous repeating dose
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
Intravenous repeating dose
Intervention Type
Drug
Intervention Name(s)
rituximab
Intervention Description
Intravenous repeating dose
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arndt Schottelius, M.D.
Organizational Affiliation
Genentech, Inc.
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
22012969
Citation
Tak PP, Rigby W, Rubbert-Roth A, Peterfy C, van Vollenhoven RF, Stohl W, Healy E, Hessey E, Reynard M, Shaw T. Sustained inhibition of progressive joint damage with rituximab plus methotrexate in early active rheumatoid arthritis: 2-year results from the randomised controlled trial IMAGE. Ann Rheum Dis. 2012 Mar;71(3):351-7. doi: 10.1136/annrheumdis-2011-200170. Epub 2011 Oct 19.
Results Reference
derived
PubMed Identifier
21557525
Citation
Rigby W, Ferraccioli G, Greenwald M, Zazueta-Montiel B, Fleischmann R, Wassenberg S, Ogale S, Armstrong G, Jahreis A, Burke L, Mela C, Chen A. Effect of rituximab on physical function and quality of life in patients with rheumatoid arthritis previously untreated with methotrexate. Arthritis Care Res (Hoboken). 2011 May;63(5):711-20. doi: 10.1002/acr.20419.
Results Reference
derived
PubMed Identifier
20937671
Citation
Tak PP, Rigby WF, Rubbert-Roth A, Peterfy CG, van Vollenhoven RF, Stohl W, Hessey E, Chen A, Tyrrell H, Shaw TM; IMAGE Investigators. Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial. Ann Rheum Dis. 2011 Jan;70(1):39-46. doi: 10.1136/ard.2010.137703. Epub 2010 Oct 11.
Results Reference
derived
Learn more about this trial
A Study to Evaluate Rituximab in Combination With Methotrexate in Methotrexate-Naive Patients With Active Rheumatoid Arthritis
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