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Trial record 6 of 9 for:    "Synovitis" | "Folate"

A Pilot Study of MabThera (Rituximab) Evaluated by MRI in Patients With Rheumatoid Arthritis.

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ClinicalTrials.gov Identifier: NCT00502853
Recruitment Status : Completed
First Posted : July 18, 2007
Results First Posted : March 12, 2015
Last Update Posted : August 16, 2017
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: rituximab [MabThera/Rituxan]
Drug: Methotrexate
Enrollment 10
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Rituximab Plus (+) Methotrexate (MTX)
Hide Arm/Group Description 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.
Period Title: Overall Study
Started 10
Completed 10
Not Completed 0
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description 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.
Overall Number of Baseline Participants 10
Hide Baseline Analysis Population Description
Safety population: all participants who received any part of an infusion of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants
52.42  (15.681)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
Female
6
  60.0%
Male
4
  40.0%
1.Primary Outcome
Title Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Synovitis Score
Hide Description 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.
Time Frame Baseline, Week 4, and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Population included all participants who received any portion of the rituximab dose and was used for efficacy and safety analyses.
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 3.4  (1.58)
Week 4 2.3  (2.75)
Change at Week 4 -1.1  (2.38)
Week 24 2.4  (1.74)
Change at Week 24 -1.0  (1.73)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline to Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1776
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline to Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1215
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Trend over time
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2246
Comments [Not Specified]
Method Random coefficient model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.1606
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1231
Estimation Comments [Not Specified]
2.Primary Outcome
Title OMERACT RAMRIS Bone Edema Score
Hide Description 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.
Time Frame Baseline, Weeks 4 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 23.2  (13.56)
Week 4 23.8  (15.68)
Change at Week 4 0.6  (14.52)
Week 24 24.0  (14.66)
Change at Week 24 0.8  (16.77)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline to Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8989
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline to Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8834
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Trend over time
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8841
Comments [Not Specified]
Method Random coefficient model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.1357
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.9051
Estimation Comments [Not Specified]
3.Primary Outcome
Title OMERACT RAMRIS Erosion Score
Hide Description 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.
Time Frame Baseline, Week 4, and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 7.9  (3.67)
Week 4 8.1  (3.63)
Change at Week 4 0.2  (1.14)
Week 24 9.1  (4.38)
Change at Week 24 1.2  (2.39)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline to Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5911
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline to Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1475
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Trend over time
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1463
Comments [Not Specified]
Method Random coefficient model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.1786
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1123
Estimation Comments [Not Specified]
4.Primary Outcome
Title Early Enhancement Rate (REE)
Hide Description 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.
Time Frame Baseline, Weeks 4 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: percent per second
Baseline 0.356  (0.2651)
Week 4 0.489  (0.5110)
Change at Week 4 0.150  (0.4106)
Week 24 0.363  (0.2615)
Change at Week 24 -0.012  (0.3227)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3358
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9158
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Trend over time
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8877
Comments [Not Specified]
Method Random coefficient model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.003418
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.02345
Estimation Comments [Not Specified]
5.Primary Outcome
Title Relative Enhancement (RE) Score
Hide Description 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).
Time Frame Baseline, Weeks 4 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: percent
Baseline 66.978  (42.3981)
Week 4 57.889  (51.9276)
Change at Week 4 -3.812  (34.3034)
Week 24 40.075  (21.6891)
Change at Week 24 -34.450  (32.9609)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7624
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0212
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Trend over time
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0712
Comments [Not Specified]
Method Random coefficient model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -4.2681
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.0529
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Ritchie Articular Index Scores
Hide Description 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).
Time Frame Baseline and Weeks 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 20.7  (8.30)
Week 4 16.9  (9.49)
Change at Week 4 -3.8  (6.78)
Week 12 9.5  (6.72)
Change at Week 12 -11.2  (6.11)
Week 24 11.7  (9.60)
Change at Week 24 -9.0  (6.50)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1101
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0018
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Trend over time
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0023
Comments [Not Specified]
Method Random coefficient model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -2.0857
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.4965
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Health Assessment Questionnaire - Disability Index (HAQ-DI) Score
Hide Description 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.
Time Frame Baseline and Weeks 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 1.788  (0.6848)
Week 4 1.471  (0.7976)
Change at Week 4 -0.316  (0.3687)
Week 12 0.838  (0.6668)
Change at Week 12 -0.950  (0.7997)
Week 24 0.888  (0.7008)
Change at Week 24 -0.900  (0.6503)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0240
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0045
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0018
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Trend over time
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0019
Comments [Not Specified]
Method Random Coefficient Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.1964
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.04524
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Patient’s Global Assessment of Pain
Hide Description 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.
Time Frame Baseline and Weeks 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: mm
Baseline 60.6  (22.75)
Week 4 49.0  (31.73)
Change at Week 4 -11.6  (20.38)
Week 12 34.7  (16.77)
Change at Week 12 -29.9  (28.27)
Week 24 22.7  (16.92)
Change at Week 24 -30.7  (23.69)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Trend over time
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0074
Comments [Not Specified]
Method Random Coefficient Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -6.6294
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.8623
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1273
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0132
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1542
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
9.Secondary Outcome
Title DAS28 Score
Hide Description 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.
Time Frame Baseline and Weeks 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 5.735  (0.8099)
Week 4 5.261  (1.5552)
Change at Week 4 -0.474  (0.9250)
Week 12 4.307  (1.4552)
Change at Week 12 -1.587  (0.9743)
Week 24 4.400  (1.4263)
Change at Week 24 -1.335  (1.1425)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1396
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0050
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0050
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Trend over time
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0054
Comments [Not Specified]
Method Random coefficient model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.2902
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.07966
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Erythrocyte Sedimentation Rate (ESR)
Hide Description 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.
Time Frame Baseline and Weeks 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: mm/hr
Baseline 72.6  (27.56)
Week 4 63.8  (26.63)
Change at Week 4 -15.6  (15.61)
Week 12 48.0  (26.12)
Change at Week 12 -30.2  (26.47)
Week 24 53.4  (18.34)
Change at Week 24 -19.1  (21.25)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0254
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0384
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0271
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Trend over time
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0124
Comments [Not Specified]
Method Random coefficient model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -4.7586
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.5278
Estimation Comments [Not Specified]
11.Secondary Outcome
Title C-Reactive Protein (CRP)
Hide Description CRP measured by milligrams per deciliter (mg/dL). High levels of CRP are indicators of active inflammation.
Time Frame Baseline and Weeks 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 21.630  (24.1805)
Week 4 23.480  (22.7518)
Change at Week 4 1.850  (16.9261)
Week 12 10.929  (12.2432)
Change at Week 12 -10.929  (18.1919)
Week 24 23.410  (26.8998)
Change at Week 24 1.780  (36.7504)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7376
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1631
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8816
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Trend over time
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8835
Comments [Not Specified]
Method Random coefficient model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.2927
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.9408
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Anti-Cyclic Citrullinated Peptide (Anti-CCP) Autoantibodies Count
Hide Description 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.
Time Frame Baseline and Weeks 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: U/mL
Baseline 55.230  (33.3902)
Week 4 44.311  (28.4448)
Change at Week 4 -10.133  (18.0815)
Week 12 41.925  (32.2708)
Change at Week 12 -12.862  (16.7306)
Week 24 122.230  (247.7763)
Change at Week 24 67.000  (247.0019)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1312
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0662
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4133
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Trend over time
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6049
Comments [Not Specified]
Method Random coefficient model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 8.8196
Parameter Dispersion
Type: Standard Error of the Mean
Value: 16.4534
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Rheumatoid Factor (RF) Immunoglobulin M (IgM) Concentrations
Hide Description 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.
Time Frame Baseline and Weeks 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: IU/mL
Baseline 570.922  (827.0900)
Week 4 307.300  (337.9550)
Change at Week 4 -285.138  (530.8209)
Week 12 241.756  (357.8067)
Change at Week 12 -329.167  (499.0426)
Week 24 281.230  (337.6633)
Change at Week 24 -267.389  (529.7928)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1725
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0832
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1685
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Trend over time
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1331
Comments [Not Specified]
Method Random coefficient model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -55.4458
Parameter Dispersion
Type: Standard Error of the Mean
Value: 33.5821
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Total Immunoglobulin (Ig) Concentrations
Hide Description Total Ig concentrations as measured by milligrams per milliliter (mg/mL).
Time Frame Baseline and Weeks 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: mg/mL
Baseline 20.258  (6.7055)
Week 4 17.786  (4.7033)
Change at Week 4 -1.602  (3.6846)
Week 12 17.296  (4.1845)
Change at Week 12 -2.336  (4.0998)
Week 24 18.354  (4.3432)
Change at Week 24 -1.042  (4.5527)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2938
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2216
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5670
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
15.Secondary Outcome
Title Hematocrit Concentration (%)
Hide Description [Not Specified]
Time Frame Baseline and Weeks 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: percentage
Baseline 36.110  (2.2218)
Week 4 37.860  (1.4315)
Change at Week 4 1.750  (2.9497)
Week 12 37.512  (2.5798)
Change at Week 12 1.350  (4.3065)
Week 24 37.967  (2.6106)
Change at Week 24 1.667  (3.6695)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0934
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4047
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2101
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Trend over time
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1451
Comments [Not Specified]
Method Random coefficient model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.3997
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2506
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Percentage of Total B-lymphocytes
Hide Description Concentration of all B-lymphocytes subtypes was assessed.
Time Frame Baseline and Weeks 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: percentage of cells
Baseline 24.040  (10.2954)
Week 4 22.430  (8.0601)
Change at Week 4 -1.610  (7.1818)
Week 12 30.125  (12.0576)
Change at Week 12 5.562  (11.6748)
Week 24 24.133  (10.2802)
Change at Week 24 1.111  (7.7194)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4963
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2198
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6773
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Trend over time
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5531
Comments [Not Specified]
Method Random coefficient model
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.3688
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.5987
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Erosion Score - Right Hand
Hide Description 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.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 2.50  (2.972)
Week 24 2.19  (2.963)
Change at Week 24 -0.44  (1.741)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5002
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
18.Secondary Outcome
Title Erosion Score - Left Hand
Hide Description 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.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population; n=number of participants with values for analysis at the specified timepoints.
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (n=10) 1.90  (2.558)
Week 24 (n=8) 1.75  (2.619)
Change at Week 24 (n=8) 0.00  (0.707)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
19.Secondary Outcome
Title Joint Space Narrowing - Right Hand
Hide Description 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).
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population; only participants with values at both Baseline and Week 24 were included in the analysis.
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 8
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 10.40  (7.859)
Week 24 10.13  (6.786)
Change at Week 24 0.94  (6.609)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7002
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
20.Secondary Outcome
Title Joint Space Narrowing - Left Hand
Hide Description 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).
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population; only participants with values at both Baseline and Week 24 were included in the analysis.
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description:
Participants received 1000 mg of Rituximab by IV infusion on Days 1 and 15 (considered to be one cycle). Participants also received 10-25 mg/week stable concomitant MTX by mouth or parenterally. Additional cycles of 2 infusions each could be administered provided the following: a minimum of 24 weeks had passed since the first infusion of the last course of study medication; the participant had a DAS28-CRP score of >2.6; the participant had a neutrophil count not below 1.5x10^3/μL; there was an absence of significant cardiac or pulmonary disease, primary or secondary immunodeficiency, and infections.
Overall Number of Participants Analyzed 8
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 8.45  (6.039)
Week 24 9.13  (6.004)
Change at Week 24 2.19  (5.694)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3132
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
21.Secondary Outcome
Title X-Rays: Right Hand Total Score
Hide Description 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).
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population; only participants with values at both Baseline and Week 24 were included in the analysis.
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 8
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 12.90  (9.433)
Week 24 12.31  (7.828)
Change at Week 24 0.50  (7.714)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8597
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
22.Secondary Outcome
Title X-Rays: Left Hand Total Score
Hide Description 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).
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population; only participants with values at both Baseline and Week 24 were included in the analysis.
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 8
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 10.35  (7.192)
Week 24 10.88  (6.813)
Change at Week 24 2.19  (6.341)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab + MTX
Comments Change from Baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3617
Comments [Not Specified]
Method Student's t-test
Comments [Not Specified]
Time Frame From baseline up to 24 weeks.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Rituximab + MTX
Hide Arm/Group Description 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.
All-Cause Mortality
Rituximab + MTX
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Rituximab + MTX
Affected / at Risk (%)
Total   2/10 (20.00%) 
Cardiac disorders   
Atrial fibrillation * 1  1/10 (10.00%) 
Infections and infestations   
Device related infection * 1  1/10 (10.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Rituximab + MTX
Affected / at Risk (%)
Total   10/10 (100.00%) 
Endocrine disorders   
Hypothyroidism * 1  1/10 (10.00%) 
Gastrointestinal disorders   
Apical granuloma * 1  1/10 (10.00%) 
Infections and infestations   
Influenza * 1  3/10 (30.00%) 
Paronychia * 1  1/10 (10.00%) 
Pharyngitis * 1  3/10 (30.00%) 
Urinary tract infection bacterial * 1  1/10 (10.00%) 
Investigations   
Alanine aminotransferase increased * 1  2/10 (20.00%) 
Metabolism and nutrition disorders   
Diabetes mellitus * 1  2/10 (20.00%) 
Musculoskeletal and connective tissue disorders   
Back pain * 1  1/10 (10.00%) 
Neck pain * 1  1/10 (10.00%) 
Osteoarthritis * 1  1/10 (10.00%) 
Tenosynovitis stenosans * 1  1/10 (10.00%) 
Nervous system disorders   
Carpal tunnel syndrome * 1  1/10 (10.00%) 
Paraesthesia * 1  1/10 (10.00%) 
Renal and urinary disorders   
Haematuria * 1  1/10 (10.00%) 
Reproductive system and breast disorders   
Amenorrhoea * 1  1/10 (10.00%) 
Skin and subcutaneous tissue disorders   
Rash pruritic * 1  1/10 (10.00%) 
Rosacea * 1  1/10 (10.00%) 
Vascular disorders   
Hypertension * 1  1/10 (10.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-LaRoche
Phone: 800-821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00502853     History of Changes
Other Study ID Numbers: ML21081
First Submitted: July 17, 2007
First Posted: July 18, 2007
Results First Submitted: July 16, 2014
Results First Posted: March 12, 2015
Last Update Posted: August 16, 2017