Trial Outcomes & Findings for A Pilot Study of MabThera (Rituximab) Evaluated by MRI in Patients With Rheumatoid Arthritis. (NCT NCT00502853)
NCT ID: NCT00502853
Last Updated: 2017-08-16
Results Overview
Extension and degree of synovitis in wrist according to RAMRIS score developed by OMERACT. Synovitis is an area in synovial compartment that shows above normal post-gadolinium enhancement of a thickness greater than width of normal synovium. Synovitis is assessed in 3 wrist regions (distal radioulnar joint; radiocarpal joint; intercarpal and carpometacarpal joints) and in each metacarpophalangeal (MCP) joint. 1st carpometacarpal joint and 1st MCP joint are not scored. Score 0 is normal, and 1-3 (mild, moderate, severe) are by thirds of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score=the sum of the individual scores (3 wrist regions \[range 0-9\] or 4 MCP joints \[range 0-12\]) for an overall range of 0-21, where 0=no damage and maximum score \[9, 12, or 21\]=most severe damage. Change in synovitis = Follow-up synovitis score - baseline score.
COMPLETED
PHASE4
10 participants
Baseline, Week 4, and Week 24
2017-08-16
Participant Flow
Participant milestones
| Measure |
Rituximab Plus (+) Methotrexate (MTX)
Participants received rituximab 1000 milligrams (mg) intravenously (IV) and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg per week (mg/week) by mouth or parenterally. Nonresponsive participants (defined as Disease Activity Score Based on 28-Joint Count and C-Reactive Protein \[DAS28-CRP\] score of greater than \[\>\]2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
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|---|---|
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Overall Study
STARTED
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10
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Overall Study
COMPLETED
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10
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Pilot Study of MabThera (Rituximab) Evaluated by MRI in Patients With Rheumatoid Arthritis.
Baseline characteristics by cohort
| Measure |
Rituximab + MTX
n=10 Participants
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
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|---|---|
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Age, Continuous
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52.42 years
STANDARD_DEVIATION 15.681 • n=5 Participants
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Sex: Female, Male
Female
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6 Participants
n=5 Participants
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Sex: Female, Male
Male
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4 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Baseline, Week 4, and Week 24Population: The Safety Population included all participants who received any portion of the rituximab dose and was used for efficacy and safety analyses.
Extension and degree of synovitis in wrist according to RAMRIS score developed by OMERACT. Synovitis is an area in synovial compartment that shows above normal post-gadolinium enhancement of a thickness greater than width of normal synovium. Synovitis is assessed in 3 wrist regions (distal radioulnar joint; radiocarpal joint; intercarpal and carpometacarpal joints) and in each metacarpophalangeal (MCP) joint. 1st carpometacarpal joint and 1st MCP joint are not scored. Score 0 is normal, and 1-3 (mild, moderate, severe) are by thirds of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score=the sum of the individual scores (3 wrist regions \[range 0-9\] or 4 MCP joints \[range 0-12\]) for an overall range of 0-21, where 0=no damage and maximum score \[9, 12, or 21\]=most severe damage. Change in synovitis = Follow-up synovitis score - baseline score.
Outcome measures
| Measure |
Rituximab + MTX
n=10 Participants
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
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Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Synovitis Score
Baseline
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3.4 units on a scale
Standard Deviation 1.58
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Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Synovitis Score
Change at Week 4
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-1.1 units on a scale
Standard Deviation 2.38
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Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Synovitis Score
Change at Week 24
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-1.0 units on a scale
Standard Deviation 1.73
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Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Synovitis Score
Week 4
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2.3 units on a scale
Standard Deviation 2.75
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Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Synovitis Score
Week 24
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2.4 units on a scale
Standard Deviation 1.74
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PRIMARY outcome
Timeframe: Baseline, Weeks 4 and 24Population: Safety Population
Extension and degree of bone edema in the wrist according to the RAMRIS score developed by OMERACT. Bone edema is a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content. Each bone (wrists: carpal bones, distal radius, distal ulna, metacarpal bases; MCP joints: metacarpal heads, phalangeal bases) is scored separately. The scale of 0-3 was based on the proportion of bone with edema, as follows: 0=no edema; 1=1 percent (%) to 33% of bone was edematous; 2 = 34%-66% of bone was edematous; and 3= 67%-100% of bone was edematous. Total bone edema score=sum of the individual scores for an overall range of 0-69, where 0=no edema and 69=most severe edema. Change in bone edema = follow-up bone edema score - baseline score.
Outcome measures
| Measure |
Rituximab + MTX
n=10 Participants
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
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OMERACT RAMRIS Bone Edema Score
Week 4
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23.8 units on a scale
Standard Deviation 15.68
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OMERACT RAMRIS Bone Edema Score
Change at Week 4
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0.6 units on a scale
Standard Deviation 14.52
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OMERACT RAMRIS Bone Edema Score
Week 24
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24.0 units on a scale
Standard Deviation 14.66
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OMERACT RAMRIS Bone Edema Score
Baseline
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23.2 units on a scale
Standard Deviation 13.56
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OMERACT RAMRIS Bone Edema Score
Change at Week 24
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0.8 units on a scale
Standard Deviation 16.77
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PRIMARY outcome
Timeframe: Baseline, Week 4, and Week 24Population: Safety Population
MRI bone erosion measures a sharply marginated bone lesion, with correct juxta-articular localization and typical signal characteristics, which is visible in 2 planes with a cortical break seen in at least 1 plane. Each bone (wrists: carpal bones, distal radius, distal ulna, metacarpal bases; MCP joints: metacarpal heads, phalangeal bases) scored separately. Scale is 0-10 based on proportion of eroded bone compared to assessed bone volume (0=no erosion; 1=1%-10% of bone eroded; 2=11%-20%, etc). For long bones, assessed bone volume is from articular surface (or best estimated position if absent) to depth of 1 centimeter (cm); in carpal bones it is the whole bone. Total erosion score=sum of individual scores for an overall range of 0-230, where 0=no erosion and 230=most severe erosion. Change in erosion=Follow-up erosion score - baseline score.
Outcome measures
| Measure |
Rituximab + MTX
n=10 Participants
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
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OMERACT RAMRIS Erosion Score
Baseline
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7.9 units on a scale
Standard Deviation 3.67
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OMERACT RAMRIS Erosion Score
Week 4
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8.1 units on a scale
Standard Deviation 3.63
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OMERACT RAMRIS Erosion Score
Week 24
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9.1 units on a scale
Standard Deviation 4.38
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OMERACT RAMRIS Erosion Score
Change at Week 24
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1.2 units on a scale
Standard Deviation 2.39
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OMERACT RAMRIS Erosion Score
Change at Week 4
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0.2 units on a scale
Standard Deviation 1.14
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PRIMARY outcome
Timeframe: Baseline, Weeks 4 and 24Population: Safety Population
A low cost, low field dedicated extremity MRI unit was used, which is specifically designed for the examination of peripheral joints. In addition to the standard OMERACT-RAMRIS scoring system, additional data were elaborated by using "dynamic" MRI, i.e. Contrast-Enhanced Dynamic MRI (DCE-MRI). This method evaluates the diffusion of the contrast mean in a series of very short sequences thus providing a diffusion curve which is proportionate to the extent of inflammation in the synovial membrane. Numerical parameters used with this method are the slope in the initial phase (rate of early enhancement - REE) and its "steady state" condition (relative enhancement - RE). REE per second during the first 55 seconds was calculated according to the formula REE55 = (S55-S0)/(S0x55)x100%. The REE shows the slope of the curve of contrast uptake tangential to the α angle and is steeper if inflammation is higher.
Outcome measures
| Measure |
Rituximab + MTX
n=10 Participants
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
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Early Enhancement Rate (REE)
Baseline
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0.356 percent per second
Standard Deviation 0.2651
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Early Enhancement Rate (REE)
Change at Week 4
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0.150 percent per second
Standard Deviation 0.4106
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Early Enhancement Rate (REE)
Week 24
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0.363 percent per second
Standard Deviation 0.2615
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Early Enhancement Rate (REE)
Change at Week 24
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-0.012 percent per second
Standard Deviation 0.3227
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Early Enhancement Rate (REE)
Week 4
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0.489 percent per second
Standard Deviation 0.5110
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PRIMARY outcome
Timeframe: Baseline, Weeks 4 and 24Population: Safety Population
A low cost, low field dedicated extremity MRI unit was used, which is specifically designed for the examination of peripheral joints. In addition to the standard OMERACT-RAMRIS scoring system, additional data were elaborated by using "dynamic" MRI (DCE-MRI). This method evaluates the diffusion of the contrast mean in a series of very short sequences thus providing a diffusion curve which is proportionate to the extent of inflammation in the synovial membrane. Numerical parameters used with this method are the slope in the initial phase (REE) and its "steady state" condition (RE).
Outcome measures
| Measure |
Rituximab + MTX
n=10 Participants
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
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Relative Enhancement (RE) Score
Week 4
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57.889 percent
Standard Deviation 51.9276
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Relative Enhancement (RE) Score
Change at Week 4
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-3.812 percent
Standard Deviation 34.3034
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Relative Enhancement (RE) Score
Baseline
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66.978 percent
Standard Deviation 42.3981
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Relative Enhancement (RE) Score
Week 24
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40.075 percent
Standard Deviation 21.6891
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Relative Enhancement (RE) Score
Change at Week 24
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-34.450 percent
Standard Deviation 32.9609
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SECONDARY outcome
Timeframe: Baseline and Weeks 4, 12, and 24Population: Safety Population
The Ritchie Articular Index is a graded assessment of tenderness in 26 joint regions. The sum of the grades of tenderness (0=not tender, 1=tender, 2=tender and causes wince, and 3 tender, causes wince and effort to withdraw) elicited by applying firm pressure over the joint margin of articular joints (such as shoulders, elbow, wrists, hips). The scores ranged from 0 (no tenderness) to 78 (most severe tenderness).
Outcome measures
| Measure |
Rituximab + MTX
n=10 Participants
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
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Ritchie Articular Index Scores
Baseline
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20.7 units on a scale
Standard Deviation 8.30
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Ritchie Articular Index Scores
Week 4
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16.9 units on a scale
Standard Deviation 9.49
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Ritchie Articular Index Scores
Change at Week 4
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-3.8 units on a scale
Standard Deviation 6.78
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Ritchie Articular Index Scores
Week 12
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9.5 units on a scale
Standard Deviation 6.72
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Ritchie Articular Index Scores
Change at Week 12
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-11.2 units on a scale
Standard Deviation 6.11
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Ritchie Articular Index Scores
Change at Week 24
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-9.0 units on a scale
Standard Deviation 6.50
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Ritchie Articular Index Scores
Week 24
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11.7 units on a scale
Standard Deviation 9.60
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SECONDARY outcome
Timeframe: Baseline and Weeks 4, 12, and 24Population: Safety Population
The Stanford HAQ-DI is a participant-reported questionnaire specific for rheumatoid arthritis (RA). It consist of 20 items referring to eight component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Each item within a domain was scored on a 4-point Likert scale from 0 to 3: 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. The highest score reported by the participant for a domain determined the score for that domain. The overall disability index is computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
Outcome measures
| Measure |
Rituximab + MTX
n=10 Participants
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
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Health Assessment Questionnaire - Disability Index (HAQ-DI) Score
Week 4
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1.471 units on a scale
Standard Deviation 0.7976
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Health Assessment Questionnaire - Disability Index (HAQ-DI) Score
Week 12
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0.838 units on a scale
Standard Deviation 0.6668
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Health Assessment Questionnaire - Disability Index (HAQ-DI) Score
Baseline
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1.788 units on a scale
Standard Deviation 0.6848
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Health Assessment Questionnaire - Disability Index (HAQ-DI) Score
Change at Week 4
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-0.316 units on a scale
Standard Deviation 0.3687
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Health Assessment Questionnaire - Disability Index (HAQ-DI) Score
Change at Week 12
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-0.950 units on a scale
Standard Deviation 0.7997
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Health Assessment Questionnaire - Disability Index (HAQ-DI) Score
Week 24
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0.888 units on a scale
Standard Deviation 0.7008
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Health Assessment Questionnaire - Disability Index (HAQ-DI) Score
Change at Week 24
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-0.900 units on a scale
Standard Deviation 0.6503
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SECONDARY outcome
Timeframe: Baseline and Weeks 4, 12, and 24Population: Safety Population
The participant's assessment of their current level of pain on a 0 to 100 millimeter (mm) horizontal VAS. The left-hand extreme of the line was described as "no pain" and the right-hand as "unbearable pain". The participant was asked to mark the line corresponding to their current level of pain and the distance from the left edge was recorded.
Outcome measures
| Measure |
Rituximab + MTX
n=10 Participants
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
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Patient's Global Assessment of Pain
Week 24
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22.7 mm
Standard Deviation 16.92
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Patient's Global Assessment of Pain
Change at Week 24
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-30.7 mm
Standard Deviation 23.69
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Patient's Global Assessment of Pain
Baseline
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60.6 mm
Standard Deviation 22.75
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Patient's Global Assessment of Pain
Week 4
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49.0 mm
Standard Deviation 31.73
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Patient's Global Assessment of Pain
Change at Week 4
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-11.6 mm
Standard Deviation 20.38
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Patient's Global Assessment of Pain
Week 12
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34.7 mm
Standard Deviation 16.77
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Patient's Global Assessment of Pain
Change at Week 12
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-29.9 mm
Standard Deviation 28.27
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SECONDARY outcome
Timeframe: Baseline and Weeks 4, 12, and 24Population: Safety Population
DAS28 calculated from the number of swollen joints and tender joints using the 28-joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hr\]) and Patient's Global Assessment of Disease Activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. A DAS28 score of less than or equal to (≤) 3.2 = low disease activity, a DAS28 score of \>3.2 to 5.1 = moderate to high disease activity.
Outcome measures
| Measure |
Rituximab + MTX
n=10 Participants
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
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DAS28 Score
Baseline
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5.735 units on a scale
Standard Deviation 0.8099
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DAS28 Score
Week 4
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5.261 units on a scale
Standard Deviation 1.5552
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DAS28 Score
Change at Week 4
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-0.474 units on a scale
Standard Deviation 0.9250
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DAS28 Score
Week 12
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4.307 units on a scale
Standard Deviation 1.4552
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DAS28 Score
Change at Week 12
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-1.587 units on a scale
Standard Deviation 0.9743
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DAS28 Score
Week 24
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4.400 units on a scale
Standard Deviation 1.4263
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DAS28 Score
Change at Week 24
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-1.335 units on a scale
Standard Deviation 1.1425
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SECONDARY outcome
Timeframe: Baseline and Weeks 4, 12, and 24Population: Safety Population
ESR was determined using the Westergren method. ESR measures how fast red blood cells (erythrocytes) fall to the bottom of a fine glass tube that is filled with the participant's blood. The higher the sedimentation rate the greater the inflammation.
Outcome measures
| Measure |
Rituximab + MTX
n=10 Participants
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
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Erythrocyte Sedimentation Rate (ESR)
Baseline
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72.6 mm/hr
Standard Deviation 27.56
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Erythrocyte Sedimentation Rate (ESR)
Week 4
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63.8 mm/hr
Standard Deviation 26.63
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Erythrocyte Sedimentation Rate (ESR)
Change at Week 4
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-15.6 mm/hr
Standard Deviation 15.61
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Erythrocyte Sedimentation Rate (ESR)
Week 12
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48.0 mm/hr
Standard Deviation 26.12
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Erythrocyte Sedimentation Rate (ESR)
Change at Week 12
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-30.2 mm/hr
Standard Deviation 26.47
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Erythrocyte Sedimentation Rate (ESR)
Week 24
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53.4 mm/hr
Standard Deviation 18.34
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Erythrocyte Sedimentation Rate (ESR)
Change at Week 24
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-19.1 mm/hr
Standard Deviation 21.25
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SECONDARY outcome
Timeframe: Baseline and Weeks 4, 12, and 24Population: Safety Population
CRP measured by milligrams per deciliter (mg/dL). High levels of CRP are indicators of active inflammation.
Outcome measures
| Measure |
Rituximab + MTX
n=10 Participants
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
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C-Reactive Protein (CRP)
Baseline
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21.630 mg/dL
Standard Deviation 24.1805
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C-Reactive Protein (CRP)
Week 4
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23.480 mg/dL
Standard Deviation 22.7518
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C-Reactive Protein (CRP)
Change at Week 4
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1.850 mg/dL
Standard Deviation 16.9261
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C-Reactive Protein (CRP)
Week 12
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10.929 mg/dL
Standard Deviation 12.2432
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C-Reactive Protein (CRP)
Change at Week 12
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-10.929 mg/dL
Standard Deviation 18.1919
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C-Reactive Protein (CRP)
Week 24
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23.410 mg/dL
Standard Deviation 26.8998
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C-Reactive Protein (CRP)
Change at Week 24
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1.780 mg/dL
Standard Deviation 36.7504
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SECONDARY outcome
Timeframe: Baseline and Weeks 4, 12, and 24Population: Safety Population
Anti-CCP autoantibodies count measured by units per milliliter (U/mL). The anti-CCP autoantibodies bind antigenic determinants that contain the unusual amino acid citrulline. The anti-CCP antibody is a highly specific diagnostic test of RA (though with variable sensitivity) and a marker of joint damage with high prognostic significance.
Outcome measures
| Measure |
Rituximab + MTX
n=10 Participants
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
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|---|---|
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Anti-Cyclic Citrullinated Peptide (Anti-CCP) Autoantibodies Count
Baseline
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55.230 U/mL
Standard Deviation 33.3902
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Anti-Cyclic Citrullinated Peptide (Anti-CCP) Autoantibodies Count
Week 4
|
44.311 U/mL
Standard Deviation 28.4448
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Anti-Cyclic Citrullinated Peptide (Anti-CCP) Autoantibodies Count
Change at Week 4
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-10.133 U/mL
Standard Deviation 18.0815
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Anti-Cyclic Citrullinated Peptide (Anti-CCP) Autoantibodies Count
Week 12
|
41.925 U/mL
Standard Deviation 32.2708
|
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Anti-Cyclic Citrullinated Peptide (Anti-CCP) Autoantibodies Count
Change at Week 12
|
-12.862 U/mL
Standard Deviation 16.7306
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Anti-Cyclic Citrullinated Peptide (Anti-CCP) Autoantibodies Count
Week 24
|
122.230 U/mL
Standard Deviation 247.7763
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Anti-Cyclic Citrullinated Peptide (Anti-CCP) Autoantibodies Count
Change at Week 24
|
67.000 U/mL
Standard Deviation 247.0019
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SECONDARY outcome
Timeframe: Baseline and Weeks 4, 12, and 24Population: Safety Population
RF IgM concentrations measured by international units per milliliter (IU/mL). RF is an antibody reacting against the fragment, crystallizable (Fc) region of IgG. Quantitative measurements have shown a prognostic value in distinguishing between progressive and non-progressive disease in early RA, a correlation with radiologically determined joint damage, and relation with clinical improvement after disease-modifying anti-rheumatic treatment.
Outcome measures
| Measure |
Rituximab + MTX
n=10 Participants
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
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|---|---|
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Rheumatoid Factor (RF) Immunoglobulin M (IgM) Concentrations
Baseline
|
570.922 IU/mL
Standard Deviation 827.0900
|
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Rheumatoid Factor (RF) Immunoglobulin M (IgM) Concentrations
Week 4
|
307.300 IU/mL
Standard Deviation 337.9550
|
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Rheumatoid Factor (RF) Immunoglobulin M (IgM) Concentrations
Change at Week 4
|
-285.138 IU/mL
Standard Deviation 530.8209
|
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Rheumatoid Factor (RF) Immunoglobulin M (IgM) Concentrations
Week 12
|
241.756 IU/mL
Standard Deviation 357.8067
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Rheumatoid Factor (RF) Immunoglobulin M (IgM) Concentrations
Change at Week 12
|
-329.167 IU/mL
Standard Deviation 499.0426
|
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Rheumatoid Factor (RF) Immunoglobulin M (IgM) Concentrations
Week 24
|
281.230 IU/mL
Standard Deviation 337.6633
|
|
Rheumatoid Factor (RF) Immunoglobulin M (IgM) Concentrations
Change at Week 24
|
-267.389 IU/mL
Standard Deviation 529.7928
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4, 12, and 24Population: Safety Population
Total Ig concentrations as measured by milligrams per milliliter (mg/mL).
Outcome measures
| Measure |
Rituximab + MTX
n=10 Participants
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
|
|---|---|
|
Total Immunoglobulin (Ig) Concentrations
Baseline
|
20.258 mg/mL
Standard Deviation 6.7055
|
|
Total Immunoglobulin (Ig) Concentrations
Week 4
|
17.786 mg/mL
Standard Deviation 4.7033
|
|
Total Immunoglobulin (Ig) Concentrations
Change at Week 4
|
-1.602 mg/mL
Standard Deviation 3.6846
|
|
Total Immunoglobulin (Ig) Concentrations
Week 12
|
17.296 mg/mL
Standard Deviation 4.1845
|
|
Total Immunoglobulin (Ig) Concentrations
Change at Week 12
|
-2.336 mg/mL
Standard Deviation 4.0998
|
|
Total Immunoglobulin (Ig) Concentrations
Week 24
|
18.354 mg/mL
Standard Deviation 4.3432
|
|
Total Immunoglobulin (Ig) Concentrations
Change at Week 24
|
-1.042 mg/mL
Standard Deviation 4.5527
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4, 12, and 24Population: Safety Population
Outcome measures
| Measure |
Rituximab + MTX
n=10 Participants
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
|
|---|---|
|
Hematocrit Concentration (%)
Baseline
|
36.110 percentage
Standard Deviation 2.2218
|
|
Hematocrit Concentration (%)
Week 4
|
37.860 percentage
Standard Deviation 1.4315
|
|
Hematocrit Concentration (%)
Change at Week 4
|
1.750 percentage
Standard Deviation 2.9497
|
|
Hematocrit Concentration (%)
Week 12
|
37.512 percentage
Standard Deviation 2.5798
|
|
Hematocrit Concentration (%)
Change at Week 12
|
1.350 percentage
Standard Deviation 4.3065
|
|
Hematocrit Concentration (%)
Week 24
|
37.967 percentage
Standard Deviation 2.6106
|
|
Hematocrit Concentration (%)
Change at Week 24
|
1.667 percentage
Standard Deviation 3.6695
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4, 12, and 24Population: Safety Population
Concentration of all B-lymphocytes subtypes was assessed.
Outcome measures
| Measure |
Rituximab + MTX
n=10 Participants
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
|
|---|---|
|
Percentage of Total B-lymphocytes
Baseline
|
24.040 percentage of cells
Standard Deviation 10.2954
|
|
Percentage of Total B-lymphocytes
Week 4
|
22.430 percentage of cells
Standard Deviation 8.0601
|
|
Percentage of Total B-lymphocytes
Change at Week 4
|
-1.610 percentage of cells
Standard Deviation 7.1818
|
|
Percentage of Total B-lymphocytes
Week 12
|
30.125 percentage of cells
Standard Deviation 12.0576
|
|
Percentage of Total B-lymphocytes
Change at Week 12
|
5.562 percentage of cells
Standard Deviation 11.6748
|
|
Percentage of Total B-lymphocytes
Week 24
|
24.133 percentage of cells
Standard Deviation 10.2802
|
|
Percentage of Total B-lymphocytes
Change at Week 24
|
1.111 percentage of cells
Standard Deviation 7.7194
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: Safety Population
The erosion score per joint of the hands can range from 0 to 5. Erosions were scored 1 if they were discrete but clearly present, and 2 or 3 if they were larger, depending on the surface area of the joint involved. A score of 3 was given if the erosion was large and extended over the imaginary middle of the bone. A score of 5 was given if a complete collapse of the joint was present or if the full surface of the joint was affected. In each joint, individual erosions were summed up to a maximum of 5. The maximal erosion score for each hand was thus 80, considering the 16 areas for erosions per hand.
Outcome measures
| Measure |
Rituximab + MTX
n=10 Participants
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
|
|---|---|
|
Erosion Score - Right Hand
Baseline
|
2.50 units on a scale
Standard Deviation 2.972
|
|
Erosion Score - Right Hand
Week 24
|
2.19 units on a scale
Standard Deviation 2.963
|
|
Erosion Score - Right Hand
Change at Week 24
|
-0.44 units on a scale
Standard Deviation 1.741
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: Safety Population; n=number of participants with values for analysis at the specified timepoints.
The erosion score per joint of the hands can range from 0 to 5. Erosions were scored 1 if they were discrete but clearly present, and 2 or 3 if they were larger, depending on the surface area of the joint involved. A score of 3 was given if the erosion was large and extended over the imaginary middle of the bone. A score of 5 was given if a complete collapse of the joint was present or if the full surface of the joint was affected. In each joint, individual erosions were summed up to a maximum of 5. The maximal erosion score for each hand was thus 80, considering the 16 areas for erosions per hand.
Outcome measures
| Measure |
Rituximab + MTX
n=10 Participants
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
|
|---|---|
|
Erosion Score - Left Hand
Baseline (n=10)
|
1.90 units on a scale
Standard Deviation 2.558
|
|
Erosion Score - Left Hand
Week 24 (n=8)
|
1.75 units on a scale
Standard Deviation 2.619
|
|
Erosion Score - Left Hand
Change at Week 24 (n=8)
|
0.00 units on a scale
Standard Deviation 0.707
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: Safety Population; only participants with values at both Baseline and Week 24 were included in the analysis.
Joint space narrowing and joint subluxation or luxation are combined in a single score with a range of 0 to 4. A normal joint space was scored 0. A score of 2 was allowed to a focal narrowing of the joint or to a joint space not sufficiently narrowed to be scored 2. The score of 1 was not to be used when the reader was unsure whether there was joint space narrowing. A generalized narrowing leaving more than 50% of the original joint space present was scored 2. A generalized narrowing leaving less than 50% of the original joint space present was scored 3, and a subluxation of a joint was also scored 3. A bony ankylosis or a complete luxation of the joint was scored 4. A total of 13 joints were evaluated for narrowing and the scores were summed (13 times \[x\] 4 \[maximum per joint\]). Each sum was normalized to a scale of 0 (best possible outcome) to 100 (worst possible outcome).
Outcome measures
| Measure |
Rituximab + MTX
n=8 Participants
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
|
|---|---|
|
Joint Space Narrowing - Right Hand
Baseline
|
10.40 units on a scale
Standard Deviation 7.859
|
|
Joint Space Narrowing - Right Hand
Week 24
|
10.13 units on a scale
Standard Deviation 6.786
|
|
Joint Space Narrowing - Right Hand
Change at Week 24
|
0.94 units on a scale
Standard Deviation 6.609
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: Safety Population; only participants with values at both Baseline and Week 24 were included in the analysis.
Joint space narrowing and joint subluxation or luxation are combined in a single score with a range of 0 to 4. A normal joint space was scored 0. A score of 2 was allowed to a focal narrowing of the joint or to a joint space not sufficiently narrowed to be scored 2. The score of 1 was not to be used when the reader was unsure whether there was joint space narrowing. A generalized narrowing leaving more than 50% of the original joint space present was scored 2. A generalized narrowing leaving less than 50% of the original joint space present was scored 3, and a subluxation of a joint was also scored 3. A bony ankylosis or a complete luxation of the joint was scored 4. A total of 13 joints were evaluated for narrowing and the scores were summed (13 x 4 \[maximum per joint\]). Each sum was normalized to a scale of 0 (best possible outcome) to 100 (worst possible outcome).
Outcome measures
| Measure |
Rituximab + MTX
n=8 Participants
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
|
|---|---|
|
Joint Space Narrowing - Left Hand
Baseline
|
8.45 units on a scale
Standard Deviation 6.039
|
|
Joint Space Narrowing - Left Hand
Week 24
|
9.13 units on a scale
Standard Deviation 6.004
|
|
Joint Space Narrowing - Left Hand
Change at Week 24
|
2.19 units on a scale
Standard Deviation 5.694
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: Safety Population; only participants with values at both Baseline and Week 24 were included in the analysis.
Right hand total scores as measured by X-rays examining erosion and joint space narrowing. Total score was calculated as the sum of the erosion score and the joint space narrowing score and scores ranged from 0 (best possible outcome) to 180 (worst possible outcome).
Outcome measures
| Measure |
Rituximab + MTX
n=8 Participants
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
|
|---|---|
|
X-Rays: Right Hand Total Score
Baseline
|
12.90 units on a scale
Standard Deviation 9.433
|
|
X-Rays: Right Hand Total Score
Week 24
|
12.31 units on a scale
Standard Deviation 7.828
|
|
X-Rays: Right Hand Total Score
Change at Week 24
|
0.50 units on a scale
Standard Deviation 7.714
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: Safety Population; only participants with values at both Baseline and Week 24 were included in the analysis.
Left hand total scores as measured by X-rays examining erosion and joint space narrowing. Total score was calculated as the sum of the erosion score and the joint space narrowing score and ranged from 0 (best possible outcome) to 180 (worst possible outcome).
Outcome measures
| Measure |
Rituximab + MTX
n=8 Participants
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
|
|---|---|
|
X-Rays: Left Hand Total Score
Baseline
|
10.35 units on a scale
Standard Deviation 7.192
|
|
X-Rays: Left Hand Total Score
Week 24
|
10.88 units on a scale
Standard Deviation 6.813
|
|
X-Rays: Left Hand Total Score
Change at Week 24
|
2.19 units on a scale
Standard Deviation 6.341
|
Adverse Events
Rituximab + MTX
Serious adverse events
| Measure |
Rituximab + MTX
n=10 participants at risk
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
|
|---|---|
|
Cardiac disorders
Atrial fibrillation
|
10.0%
1/10 • From baseline up to 24 weeks.
|
|
Infections and infestations
Device related infection
|
10.0%
1/10 • From baseline up to 24 weeks.
|
Other adverse events
| Measure |
Rituximab + MTX
n=10 participants at risk
Participants received rituximab 1000 mg IV and methylprednisolone 100 mg IV on Days 1 and 15 and MTX at a stable dose of 10-25 mg/week by mouth or parenterally. Nonresponsive participants (defined as DAS28-CRP score of \>2.6) could have received additional infusions of rituximab 1000 mg (2 infusions, 14 days apart) provided a minimum of 24 weeks had passed since the first infusion of the last course of study medication.
|
|---|---|
|
Endocrine disorders
Hypothyroidism
|
10.0%
1/10 • From baseline up to 24 weeks.
|
|
Gastrointestinal disorders
Apical granuloma
|
10.0%
1/10 • From baseline up to 24 weeks.
|
|
Infections and infestations
Influenza
|
30.0%
3/10 • From baseline up to 24 weeks.
|
|
Infections and infestations
Paronychia
|
10.0%
1/10 • From baseline up to 24 weeks.
|
|
Infections and infestations
Pharyngitis
|
30.0%
3/10 • From baseline up to 24 weeks.
|
|
Infections and infestations
Urinary tract infection bacterial
|
10.0%
1/10 • From baseline up to 24 weeks.
|
|
Investigations
Alanine aminotransferase increased
|
20.0%
2/10 • From baseline up to 24 weeks.
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
20.0%
2/10 • From baseline up to 24 weeks.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.0%
1/10 • From baseline up to 24 weeks.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
10.0%
1/10 • From baseline up to 24 weeks.
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
10.0%
1/10 • From baseline up to 24 weeks.
|
|
Musculoskeletal and connective tissue disorders
Tenosynovitis stenosans
|
10.0%
1/10 • From baseline up to 24 weeks.
|
|
Nervous system disorders
Carpal tunnel syndrome
|
10.0%
1/10 • From baseline up to 24 weeks.
|
|
Nervous system disorders
Paraesthesia
|
10.0%
1/10 • From baseline up to 24 weeks.
|
|
Renal and urinary disorders
Haematuria
|
10.0%
1/10 • From baseline up to 24 weeks.
|
|
Reproductive system and breast disorders
Amenorrhoea
|
10.0%
1/10 • From baseline up to 24 weeks.
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
10.0%
1/10 • From baseline up to 24 weeks.
|
|
Skin and subcutaneous tissue disorders
Rosacea
|
10.0%
1/10 • From baseline up to 24 weeks.
|
|
Vascular disorders
Hypertension
|
10.0%
1/10 • From baseline up to 24 weeks.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER