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A Study to Evaluate the Safety and Efficacy of MabThera (Rituximab) in Combination With Methotrexate (MTX) in Participants With Active Rheumatoid Arthritis Who Failed on Anti-Tumor Necrosis Factor Alpha Therapy

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ClinicalTrials.gov Identifier: NCT00468546
Recruitment Status : Completed
First Posted : May 2, 2007
Results First Posted : October 25, 2016
Last Update Posted : October 25, 2016
Sponsor:
Collaborator:
Biogen
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double;   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: MabThera/Rituxan
Drug: Methotrexate
Other: Placebo
Enrollment 520
Recruitment Details A total of 520 participants were enrolled in the study conducted from 02 May 2003 and 12 July 2012 in 11 countries.
Pre-assignment Details Of the total randomized 520 participants who met the eligibility criteria, four did not receive the study treatment and were not included in any analysis population.
Arm/Group Title Placebo Plus Methotrexate Rituximab Plus Methotrexate
Hide Arm/Group Description Eligible participants were administered the placebo by intravenous infusion on Days 1 and 15 along with methotrexate (MTX) 10-25 milligrams (mg) per os (p.o.) or parenterally once a week up to Week 24 and were followed up to Week 104. Eligible Participants were administered rituximab 1000 mg as intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to Week 24 and were followed up to Week 104.
Period Title: Week 24 Analysis
Started 208 308
Completed 111 253
Not Completed 97 55
Reason Not Completed
Lack of Efficacy             83             37
Refused treatment             5             5
Adverse Event             1             8
Failure to return             3             4
Rescue therapy             2             0
Incorrect diagnosis and treatment             0             1
Due to clinical hold             1             0
Went onto rescue therapy             1             0
Participant unblinded (clinical hold)             1             0
Period Title: Week 24 to Week 104 Analysis
Started 208 [1] 308 [2]
Completed 103 83
Not Completed 105 225
Reason Not Completed
Adverse Event             2             5
Death             1             0
Lack of Efficacy             3             12
Protocol Violation             0             2
Refused treatment             4             7
Failure to return             1             2
Movement into re-treatment study             77             183
Other             17             14
[1]
Participants who completed/not completed Week (W) 24 analysis were entered in W24 to W104 analysis.
[2]
Participants who completed/not completed W24 analysis were entered in W24 to W104 analysis.
Arm/Group Title Placebo Plus Methotrexate Rituximab Plus Methotrexate Total
Hide Arm/Group Description Eligible participants were administered placebo by intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to 24 weeks and were followed up to Week 104. Eligible Participants were administered rituximab 1000 mg as intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to Week 24 and were followed up to Week 104. Total of all reporting groups
Overall Number of Baseline Participants 208 308 516
Hide Baseline Analysis Population Description
Safety population included participants who were randomized and received any part of an infusion of the study drug.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 208 participants 308 participants 516 participants
55.0
(20 to 79)
53.0
(20 to 81)
53.0
(20 to 81)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 208 participants 308 participants 516 participants
Female
168
  80.8%
251
  81.5%
419
  81.2%
Male
40
  19.2%
57
  18.5%
97
  18.8%
1.Primary Outcome
Title Number of Participants With American College of Rheumatology 20 Response at Week 24
Hide Description American College of Rheumatology (ACR) 20 response is defined as >= 20% improvement (reduction) in score compared with baseline for both tender joint count (TJC)-68 joints and swollen joint count (SJC)-66 joints, as well as for 3 of the additional 5 ACR core set variables: Patient’s Assessment of Pain over the previous 24 hours using a Visual Analog Scale (VAS) ranging from score 0 (no pain) to 100 (unbearable pain); Patient’s Global Assessment of Disease Activity and Physician’s Global Assessment of Disease Activity over the previous 24 hours using a VAS ranging score 0 (no disease activity) to 100 (maximum disease activity); Health Assessment Questionnaire (HAQ):8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities) rated on a 4-point scale (0=without any difficulty to 3=unable to do) for a total possible score of 0 (best) to 3 (worst); and acute-phase reactant, either C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR).
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population included all randomized participants who received any part of an infusion of study drug. Participants whom treatment allocation was unblinded and who received treatment prior to randomization were excluded.
Arm/Group Title Placebo Plus Methotrexate Rituximab Plus Methotrexate
Hide Arm/Group Description:
Eligible participants were administered placebo by intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to 24 weeks and were followed up to Week 104.
Eligible Participants were administered rituximab 1000 mg as intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to Week 24 and were followed up to Week 104.
Overall Number of Participants Analyzed 201 298
Measure Type: Number
Unit of Measure: participants
36 153
2.Secondary Outcome
Title Number of Participants With an ACR 50 Response at Week 24
Hide Description ACR 50 response is defined as a >= 50% improvement (reduction) in score compared with baseline for both TJC -68 joints and SJC -66 joints, as well as for 3 of the additional 5 ACR core set variables: Patient’s Assessment of Pain over the previous 24 hours: using a VAS ranging from score '0'=no pain to score '100'=unbearable pain; Patient’s Global Assessment of Disease Activity and Physician’s Global Assessment of Disease Activity over the previous 24 hours using a VAS ranging from score '0'=no disease activity to score '100'=maximum disease activity; HAQ : Health Assessment Questionnaire (HAQ):which included 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities) rated on a 4-point scale (0=without any difficulty to 3=unable to do), where the sum of scores was divided by the number of domains with a score for a total possible score of 0 (best) to 3 (worst); and acute-phase reactant, either CRP or ESR.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants who received any part of an infusion of study drug. Participants whom treatment allocation was unblinded and who received treatment prior to randomization were excluded.
Arm/Group Title Placebo Plus Methotrexate Rituximab Plus Methotrexate
Hide Arm/Group Description:
Eligible participants were administered placebo by intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to 24 weeks and were followed up to Week 104.
Eligible Participants were administered rituximab 1000 mg as intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to Week 24 and were followed up to Week 104.
Overall Number of Participants Analyzed 201 298
Measure Type: Number
Unit of Measure: participants
11 80
3.Secondary Outcome
Title Number of Participants With ACR 70 Response at Week 24
Hide Description ACR 70 response is defined as a >= 70% improvement (reduction) in score compared with baseline for both TJC -68 joints and SJC -66 joints, as well as for 3 of the additional 5 ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a VAS ranging from score '0'=no pain to score '100'=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS ranging from score '0'=no disease activity to score '100'=maximum disease activity; HAQ : Health Assessment Questionnaire (HAQ):which included 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities) rated on a 4-point scale (0=without any difficulty to 3=unable to do), where the sum of scores was divided by the number of domains with a score for a total possible score of 0 (best) to 3 (worst); and acute-phase reactant, either CRP or ESR.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants who received any part of an infusion of study drug. Participants whom treatment allocation was unblinded and who received treatment prior to randomization were excluded.
Arm/Group Title Placebo Plus Methotrexate Rituximab Plus Methotrexate
Hide Arm/Group Description:
Eligible participants were administered placebo by intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to 24 weeks and were followed up to Week 104.
Eligible Participants were administered rituximab 1000 mg as intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to Week 24 and were followed up to Week 104.
Overall Number of Participants Analyzed 201 298
Measure Type: Number
Unit of Measure: participants
3 37
4.Secondary Outcome
Title Mean Change From Baseline in Disease Activity Score of 28 Joints at Week 24
Hide Description The disease activity score (DAS28) is an evaluation index of rheumatoid arthritis. The DAS28 applies a mathematical formula based on the following parameters: 1. TJC-28 joints, 2. SJC -28 joints, 3. ESR or CRP measurement, 4. Participant’s judgement on his own overall health (global health [GH]) status expressed by a VAS (0 [no disease activity] to 100 [maximum disease activity]). The mathematical formula is 0.56 × √28TJC + 0.28 × √28SJC + 0.7 x loge ESR + 0.014 × GH. The DAS28 scale ranges from score of 0 to 10, where lower scores indicate best disease control and higher scores indicate worsening of disease. Change from Baseline = difference between the score at Week 24 and the score at Baseline.
Time Frame From Baseline (Day 1) to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants who received any part of an infusion of study drug. Participants whom treatment allocation was unblinded and who received treatment prior to randomization were excluded.
Arm/Group Title Placebo Plus Methotrexate Rituximab Plus Methotrexate
Hide Arm/Group Description:
Eligible participants were administered placebo by intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to 24 weeks and were followed up to Week 104.
Eligible Participants were administered rituximab 1000 mg as intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to Week 24 and were followed up to Week 104.
Overall Number of Participants Analyzed 201 298
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.4  (1.17) -1.9  (1.60)
5.Secondary Outcome
Title Percentage of Participants With DAS28 Low Disease Activity and DAS28 Remission at Week 24
Hide Description The DAS28 is an evaluation index of RA. The DAS28 applies a mathematical formula based on the following parameters: 1. TJC- 28 joints, 2. SJC- 28 joints, 3. ESR or CRP measurement, 4. Participant’s judgement on his own overall health status (GH) expressed by a visual analogue scale VAS (0 [no disease activity] to 100 [maximum disease activity]). The mathematical formula is 0.56 × √28TJC + 0.28 × √28SJC + 0.7 x loge ESR + 0.014 × GH. The DAS28 scale ranges from score of 0 to 10. A participant was categorized as having low disease activity, if participant’s DAS28 score was <= 3.2, and was categorized as having clinical remission if participant’s DAS28 score was < 2.6.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants who received any part of an infusion of study drug. Participants whom treatment allocation was unblinded and who received treatment prior to randomization were excluded.
Arm/Group Title Placebo Plus Methotrexate Rituximab Plus Methotrexate
Hide Arm/Group Description:
Eligible participants were administered placebo by intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to 24 weeks and were followed up to Week 104.
Eligible Participants were administered rituximab 1000 mg as intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to Week 24 and were followed up to Week 104.
Overall Number of Participants Analyzed 201 298
Measure Type: Number
Unit of Measure: percentage of participants
Low disease activity 2 15
Remission 0 9
6.Secondary Outcome
Title Number of Participants With Good, Moderate, or no European League Against Rheumatism Responses at Week 24
Hide Description European League Against Rheumatism (EULAR) response is defined based on the DAS28 score and the EULAR response criteria (Van Gestel et al, 1996 and 1999). The DAS28 scale ranges from score of 0 to 10, where lower scores indicate best disease control and higher scores indicate worsening of disease. At a given visit, participants with a DAS28 score of < 3.2 are considered good responders if the change from baseline in their DAS28 score is >1.2. Participants with a DAS28 score >= 3.2 to 5.1 are considered moderate responders if the change from baseline in their DAS28 score is <=1.2 to >=0.6. Participants with DAS28 score >5.1 are considered non-responders if the change from baseline in their DAS28 score is <=1.2 to >=0.6.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants who received any part of an infusion of study drug. Participants whom treatment allocation was unblinded and who received treatment prior to randomization were excluded.
Arm/Group Title Placebo Plus Methotrexate Rituximab Plus Methotrexate
Hide Arm/Group Description:
Eligible participants were administered placebo by intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to 24 weeks and were followed up to Week 104.
Eligible Participants were administered rituximab 1000 mg as intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to Week 24 and were followed up to Week 104.
Overall Number of Participants Analyzed 201 298
Measure Type: Number
Unit of Measure: participants
No response 157 105
Moderate response 40 149
Good response 4 44
7.Secondary Outcome
Title Percentage Change From Baseline in the ACR Core Set (SJC, TJC, Patient’s and Physician’s Global Assessments, Health Assessment Questionnaire, Pain, C-Reactive Protein, and Erythrocyte Sedimentation Rate) Score
Hide Description Percentage change in the scores of the following parameters of ACR core set relative to respective baseline scores in both study arms was analyzed : SJC (28 and 66 joints) and TJC (28 and 66 joints), patient’s global assessment and physician’s global assessment based on disease activity (both are expressed by VAS [0 = no disease activity to 100 = maximum disease activity]), HAQ (based on HAQ disability index [HAQDI]) which included 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities) rated on a 4-point scale (0=without any difficulty to 3=unable to do), where the sum of scores was divided by the number of domains with a score for a total possible score of 0 (best) to 3 (worst), pain assessment using a VAS ranging from score 0 (no pain) to 100 (unbearable pain), CRP concentration, and ESR.
Time Frame From Baseline (Day 1) to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants who received any part of an infusion of study drug. Participants whom treatment allocation was unblinded and who received treatment prior to randomization were excluded.
Arm/Group Title Placebo Plus Methotrexate Rituximab Plus Methotrexate
Hide Arm/Group Description:
Eligible participants were administered placebo by intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to 24 weeks and were followed up to Week 104.
Eligible Participants were administered rituximab 1000 mg as intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to Week 24 and were followed up to Week 104.
Overall Number of Participants Analyzed 201 298
Mean (Standard Deviation)
Unit of Measure: percent change
SJC (66) -5.6  (59.19) -43.0  (52.65)
SJC (28) -7.1  (55.35) -41.3  (52.77)
TJC (68) 7.2  (144.58) -41.8  (52.39)
TJC (28) 15.7  (195.94) -42.0  (63.47)
Physician’s global assessment -4.2  (47.23) -40.8  (39.31)
Patient’s global assessment -3.1  (44.01) -25.4  (117.90)
Patient’s pain assessment 2.8  (55.61) -23.8  (131.59)
HAQ -2.0  (30.46) -24.3  (34.92)
CRP 80.0  (452.94) -36.3  (80.3)
ESR 11.4  (95.95) -29.3  (59.92)
8.Secondary Outcome
Title Mean Change From Baseline of Short Form 36 Total Scores at Week 24
Hide Description The Short Form (SF)-36 determined participants’ overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual daily activities because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems since last month; 7) limitations in usual work (house hold and outside) due to emotional problems 8) current and 1 year past status of health 9) general mental health. Transforming and standardizing these domains leads to the calculation of the physical component summary and mental component summary measures. Scores on each item were summed and averaged (range 0 [worst] to 100 [best]); increase in score from baseline indicated improvement. Change from Baseline = difference between the score at Week 24 and the score at Baseline.
Time Frame From Baseline (Day 1) to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants who received any part of an infusion of study drug. Participants with available data at the time of evaluation were analyzed.
Arm/Group Title Placebo Plus Methotrexate Rituximab Plus Methotrexate
Hide Arm/Group Description:
Eligible participants were administered placebo by intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to 24 weeks and were followed up to Week 104.
Eligible Participants were administered rituximab 1000 mg as intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to Week 24 and were followed up to Week 104.
Overall Number of Participants Analyzed 197 294
Mean (Standard Deviation)
Unit of Measure: units on a scale
Physical score 0.9  (5.65) 5.8  (8.47)
Mental health score 1.3  (9.43) 4.7  (11.75)
9.Secondary Outcome
Title Number of Participants With Categorical Change From Baseline in the Physical Component Scores of SF-36
Hide Description The SF-36 determined participants’ overall quality of life by assessing :1) limitations in physical functioning due to health problems; 2) limitations in usual daily activities because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems since last month; 7) limitations in usual work (house hold and outside) due to emotional problems 8) current and 1 year past status of health 9) general mental health. Scores on physical component were summed and averaged (range 0 [worst] to 100 [best]); If participants’ had shown change from baseline in physical health component score >5.42, it was considered as improved; score between -5.42 to 5.42 was considered as unchanged, and score < -5.42 was considered as worsened. Change from Baseline = difference between the score of physical component at Week 24 and the score at Baseline.
Time Frame From Baseline (Day 1) to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants who received any part of an infusion of study drug. Participants with available data at the time of evaluation were analyzed.
Arm/Group Title Placebo Plus Methotrexate Rituximab Plus Methotrexate
Hide Arm/Group Description:
Eligible participants were administered placebo by intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to 24 weeks and were followed up to Week 104.
Eligible Participants were administered rituximab 1000 mg as intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to Week 24 and were followed up to Week 104.
Overall Number of Participants Analyzed 197 294
Measure Type: Number
Unit of Measure: participants
Improved 25 141
Unchanged 158 136
Worsened 14 17
10.Secondary Outcome
Title Number of Participants With Change From Baseline in the Mental Component Scores of SF-36
Hide Description The SF-36 determined participants’ overall quality of life by assessing :1) limitations in physical functioning due to health problems; 2) limitations in usual daily activities because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems since last month; 7) limitations in usual work (house hold and outside) due to emotional problems 8) current and 1 year past status of health 9) general mental health. Scores on mental component were summed and averaged (range = 0 [worst]-100 [best]); increase from baseline indicated improvement. If participants’ had shown change from baseline in mental health score >6.33, it was considered as improved; scores between -6.33 to 6.33 was considered unchanged, and score <-6.33 was considered as worsened. Change from Baseline = difference between the mental component score at Week 24 and the score at Baseline.
Time Frame From Baseline (Day 1) to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants who received any part of an infusion of study drug. Participants with available data at the time of evaluation were analyzed.
Arm/Group Title Placebo Plus Methotrexate Rituximab Plus Methotrexate
Hide Arm/Group Description:
Eligible participants were administered placebo by intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to 24 weeks and were followed up to Week 104.
Eligible Participants were administered rituximab 1000 mg as intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to Week 24 and were followed up to Week 104.
Overall Number of Participants Analyzed 197 294
Measure Type: Number
Unit of Measure: participants
Improved 40 111
Unchanged 128 144
Worsened 29 39
11.Secondary Outcome
Title Mean Change From Baseline in the Genant-modified Sharp Joint Space Narrowing Score, Genant-modified Sharp Total Score, and Erosion Score
Hide Description The Genant-modified Sharp scoring system assesses structural damage due to rheumatoid arthritis in radiographs. A score for erosions of 0-3.5 (8 gradations) is assigned for 14 joints in each hand and wrist, and 6 joints in each foot. Joint space narrowing scores of 0-4 (9 gradations) are assigned to 13 joints in each hand and 6 joints in each foot. The maximum erosion score is 40 x 3.5 = 140. The maximum joint space narrowing score is 38 x 4.0 = 152. Both the erosion and joint space narrowing scores are normalized to 145 and are added together for a maximum total Genant-modified Sharp score of 290. For all the three radiograph assessment, the minimum score is 0. A higher score indicates more damage and a negative change score indicates improvement. The change in score is to be calculated as: Change from Baseline = difference between the score at Weeks 24, 56, or 104 and the score at Baseline.
Time Frame From Baseline (Day 1) to Weeks (W) 24, 56, and 104
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all randomized participants who received any part of an infusion of study drug. Participants whom treatment allocation was unblinded and who received treatment prior to randomization were excluded.
Arm/Group Title Placebo Plus Methotrexate Rituximab Plus Methotrexate
Hide Arm/Group Description:
Eligible participants were administered placebo by intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to 24 weeks and were followed up to Week 104.
Eligible Participants were administered rituximab 1000 mg as intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to Week 24 and were followed up to Week 104.
Overall Number of Participants Analyzed 201 298
Mean (Standard Deviation)
Unit of Measure: units on a scale
Sharp-Genant total score, W24, n = 201, 298 -4.3  (24.09) -1.2  (20.90)
Sharp-Genant total score, W56, n = 184, 273 2.31  (5.283) 1.00  (2.751)
Sharp-Genant total score, W104, n = 186,279 2.82  (6.398) 1.16  (3.429)
Erosion score, W24, n = 201, 298 -1.6  (12.15) -0.4  (10.45)
Erosion score, W56, n = 184, 273 1.32  (3.155) 0.59  (1.843)
Erosion score, W104, n = 186,279 1.81  (4.187) 0.73  (2.262)
Joint space narrowing score, W24, n = 201, 298 -2.5  (12.71) -0.9  (10.90)
Joint space narrowing score, W56, n = 184, 273 0.99  (2.571) 0.41  (1.323)
Joint space narrowing score, W104, n = 186,279 1.01  (2.618) 0.43  (1.563)
12.Secondary Outcome
Title Percentage of Participants Without Erosive Progression
Hide Description The Genant-modified Sharp scoring system assesses structural damage due to rheumatoid arthritis in radiographs. A score for erosions of 0-3.5 (8 gradations) is assigned for 14 joints in each hand and wrist, and 6 joints in each foot. The maximum erosion score is 40 x 3.5 = 140 which is normalized to 145. The minimum score is 0 and the maximum score is 145. A higher score indicates more damage and negative change score indicates improvement.
Time Frame Up to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants who received any part of an infusion of study medication. Participants with available data at the time of evaluation were analyzed.
Arm/Group Title Placebo Plus Methotrexate Rituximab Plus Methotrexate
Hide Arm/Group Description:
Eligible participants were administered placebo by intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to 24 weeks and were followed up to Week 104.
Eligible Participants were administered rituximab 1000 mg as intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to Week 24 and were followed up to Week 104.
Overall Number of Participants Analyzed 187 281
Measure Type: Number
Unit of Measure: percentage of participants
Baseline to Year 1, n = 186, 278 51 66
Year 1 to Year 2, n = 186, 278 58 73
Baseline to Year 2, n = 187, 281 44 60
Time Frame Up to Week 104
Adverse Event Reporting Description Adverse events were captured in safety analysis population. Safety population included participants who were randomized and received any part of an infusion of the study drug.
 
Arm/Group Title Placebo Plus Methotrexate Rituximab Plus Methotrexate
Hide Arm/Group Description Eligible participants were administered placebo by intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to 24 weeks and were followed up to Week 104. Eligible Participants were administered rituximab 1000 mg as intravenous infusion on Days 1 and 15 along with MTX 10-25 mg p.o. or parenterally once a week up to Week 24 and were followed up to Week 104.
All-Cause Mortality
Placebo Plus Methotrexate Rituximab Plus Methotrexate
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Plus Methotrexate Rituximab Plus Methotrexate
Affected / at Risk (%) Affected / at Risk (%)
Total   26/208 (12.50%)   50/308 (16.23%) 
Blood and lymphatic system disorders     
Anaemia  1  1/208 (0.48%)  0/308 (0.00%) 
Lymphadenopathy  1  0/208 (0.00%)  1/308 (0.32%) 
Cardiac disorders     
Myocardial infarction  1  1/208 (0.48%)  3/308 (0.97%) 
Angina pectoris  1  1/208 (0.48%)  1/308 (0.32%) 
Angina unstable  1  1/208 (0.48%)  1/308 (0.32%) 
Atrial fibrillation  1  0/208 (0.00%)  1/308 (0.32%) 
Atrioventricular block complete  1  0/208 (0.00%)  1/308 (0.32%) 
Cardiac arrest  1  1/208 (0.48%)  0/308 (0.00%) 
Cardiac failure  1  0/208 (0.00%)  1/308 (0.32%) 
Cardiac tamponade  1  0/208 (0.00%)  1/308 (0.32%) 
Cardiomyopathy  1  0/208 (0.00%)  1/308 (0.32%) 
Pericarditis  1  1/208 (0.48%)  0/308 (0.00%) 
Gastrointestinal disorders     
Diarrhoea  1  0/208 (0.00%)  1/308 (0.32%) 
Gastric ulcer  1  0/208 (0.00%)  1/308 (0.32%) 
Gastrointestinal haemorrhage  1  0/208 (0.00%)  1/308 (0.32%) 
Gastrooesophageal reflux disease  1  0/208 (0.00%)  1/308 (0.32%) 
Nausea  1  0/208 (0.00%)  1/308 (0.32%) 
Pancreatitis  1  1/208 (0.48%)  0/308 (0.00%) 
Vomiting  1  0/208 (0.00%)  1/308 (0.32%) 
General disorders     
Chest pain  1  1/208 (0.48%)  0/308 (0.00%) 
Pyrexia  1  0/208 (0.00%)  1/308 (0.32%) 
Immune system disorders     
Anaphylactic reaction  1  0/208 (0.00%)  1/308 (0.32%) 
Infections and infestations     
Pneumonia  1  0/208 (0.00%)  3/308 (0.97%) 
Cellulitis  1  0/208 (0.00%)  2/308 (0.65%) 
Diverticulitis  1  0/208 (0.00%)  2/308 (0.65%) 
Escherichia urinary tract infection  1  0/208 (0.00%)  2/308 (0.65%) 
Abscess intestinal  1  1/208 (0.48%)  0/308 (0.00%) 
Bronchitis  1  0/208 (0.00%)  1/308 (0.32%) 
Cellulitis gangrenous  1  0/208 (0.00%)  1/308 (0.32%) 
Device related infection  1  1/208 (0.48%)  0/308 (0.00%) 
Empyema  1  0/208 (0.00%)  1/308 (0.32%) 
Erysipelas  1  0/208 (0.00%)  1/308 (0.32%) 
Gastroenteritis  1  0/208 (0.00%)  1/308 (0.32%) 
Gastroenteritis viral  1  0/208 (0.00%)  1/308 (0.32%) 
Hepatitis B  1  0/208 (0.00%)  1/308 (0.32%) 
Infection  1  0/208 (0.00%)  1/308 (0.32%) 
Influenza  1  0/208 (0.00%)  1/308 (0.32%) 
Meningitis viral  1  0/208 (0.00%)  1/308 (0.32%) 
Pyelonephritis  1  0/208 (0.00%)  1/308 (0.32%) 
Sepsis  1  0/208 (0.00%)  1/308 (0.32%) 
Zoonosis  1  0/208 (0.00%)  1/308 (0.32%) 
Injury, poisoning and procedural complications     
Fall  1  2/208 (0.96%)  0/308 (0.00%) 
Joint dislocation  1  1/208 (0.48%)  0/308 (0.00%) 
Tibia fracture  1  0/208 (0.00%)  1/308 (0.32%) 
Investigations     
International normalised ratio increased  1  0/208 (0.00%)  1/308 (0.32%) 
Metabolism and nutrition disorders     
Hyperkalaemia  1  0/208 (0.00%)  1/308 (0.32%) 
Type 2 diabetes mellitus  1  1/208 (0.48%)  0/308 (0.00%) 
Musculoskeletal and connective tissue disorders     
Rheumatoid arthritis  1  5/208 (2.40%)  6/308 (1.95%) 
Osteoarthritis  1  0/208 (0.00%)  2/308 (0.65%) 
Arthralgia  1  1/208 (0.48%)  0/308 (0.00%) 
Back pain  1  1/208 (0.48%)  0/308 (0.00%) 
Bursitis  1  0/208 (0.00%)  1/308 (0.32%) 
Cervical spinal stenosis  1  0/208 (0.00%)  1/308 (0.32%) 
Intervertebral disc degeneration  1  0/208 (0.00%)  1/308 (0.32%) 
Intervertebral disc protrusion  1  0/208 (0.00%)  1/308 (0.32%) 
Monarthritis  1  0/208 (0.00%)  1/308 (0.32%) 
Neck pain  1  1/208 (0.48%)  0/308 (0.00%) 
Polyarthritis  1  0/208 (0.00%)  1/308 (0.32%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Breast cancer  1  1/208 (0.48%)  0/308 (0.00%) 
Gastric cancer  1  1/208 (0.48%)  0/308 (0.00%) 
Intestinal adenocarcinoma  1  0/208 (0.00%)  1/308 (0.32%) 
Pancreatic carcinoma  1  0/208 (0.00%)  1/308 (0.32%) 
Prostate cancer  1  0/208 (0.00%)  1/308 (0.32%) 
Nervous system disorders     
Syncope  1  0/208 (0.00%)  2/308 (0.65%) 
Cerebrovascular accident  1  0/208 (0.00%)  1/308 (0.32%) 
Spinal cord compression  1  0/208 (0.00%)  1/308 (0.32%) 
Transient ischaemic attack  1  0/208 (0.00%)  1/308 (0.32%) 
Pregnancy, puerperium and perinatal conditions     
Abortion spontaneous  1  0/208 (0.00%)  2/308 (0.65%) 
Pregnancy  1  1/208 (0.48%)  1/308 (0.32%) 
Psychiatric disorders     
Confusional state  1  0/208 (0.00%)  1/308 (0.32%) 
Suicide attempt  1  0/208 (0.00%)  1/308 (0.32%) 
Renal and urinary disorders     
Acute prerenal failure  1  0/208 (0.00%)  1/308 (0.32%) 
Renal failure chronic  1  0/208 (0.00%)  1/308 (0.32%) 
Respiratory, thoracic and mediastinal disorders     
Pleurisy  1  1/208 (0.48%)  1/308 (0.32%) 
Chronic obstructive pulmonary disease  1  0/208 (0.00%)  1/308 (0.32%) 
Interstitial lung disease  1  0/208 (0.00%)  1/308 (0.32%) 
Mediastinal mass  1  0/208 (0.00%)  1/308 (0.32%) 
Pleuritic pain  1  0/208 (0.00%)  1/308 (0.32%) 
Skin and subcutaneous tissue disorders     
Skin ulcer  1  0/208 (0.00%)  1/308 (0.32%) 
Subcutaneous nodule  1  1/208 (0.48%)  0/308 (0.00%) 
Surgical and medical procedures     
Synovectomy  1  1/208 (0.48%)  0/308 (0.00%) 
Vascular disorders     
Deep vein thrombosis  1  1/208 (0.48%)  3/308 (0.97%) 
Hypertension  1  1/208 (0.48%)  3/308 (0.97%) 
Vasculitis  1  1/208 (0.48%)  0/308 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, 15.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Plus Methotrexate Rituximab Plus Methotrexate
Affected / at Risk (%) Affected / at Risk (%)
Total   152/208 (73.08%)   225/308 (73.05%) 
Gastrointestinal disorders     
Diarrhoea  1  18/208 (8.65%)  21/308 (6.82%) 
Nausea  1  8/208 (3.85%)  23/308 (7.47%) 
General disorders     
Fatigue  1  12/208 (5.77%)  21/308 (6.82%) 
Pyrexia  1  7/208 (3.37%)  17/308 (5.52%) 
Infections and infestations     
Upper Respiratory Tract infection  1  17/208 (8.17%)  36/308 (11.69%) 
Nasopharyngitis  1  15/208 (7.21%)  30/308 (9.74%) 
Bronchitis  1  15/208 (7.21%)  25/308 (8.12%) 
Urinary Tract Infection  1  15/208 (7.21%)  21/308 (6.82%) 
Sinusitis  1  14/208 (6.73%)  12/308 (3.90%) 
Musculoskeletal and connective tissue disorders     
Rheumatoid Arthritis  1  87/208 (41.83%)  106/308 (34.42%) 
Arthralgia  1  8/208 (3.85%)  24/308 (7.79%) 
Back Pain  1  10/208 (4.81%)  16/308 (5.19%) 
Nervous system disorders     
Headache  1  21/208 (10.10%)  31/308 (10.06%) 
Dizziness  1  8/208 (3.85%)  16/308 (5.19%) 
Psychiatric disorders     
Insomnia  1  9/208 (4.33%)  17/308 (5.52%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  11/208 (5.29%)  12/308 (3.90%) 
Skin and subcutaneous tissue disorders     
Rash  1  9/208 (4.33%)  16/308 (5.19%) 
Vascular disorders     
Hypertension  1  12/208 (5.77%)  26/308 (8.44%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, 15.1
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
Name/Title: Roche Trial Information Hotline
Organization: F. Hoffmann-La Roche AG
Phone: +41 616878333
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00468546     History of Changes
Other Study ID Numbers: WA17042
102-20 ( Other Identifier: registry identifier )
First Submitted: April 30, 2007
First Posted: May 2, 2007
Results First Submitted: August 30, 2016
Results First Posted: October 25, 2016
Last Update Posted: October 25, 2016