Trial Outcomes & Findings for A Study of Rituximab (MabThera®/Rituxan®) in Patients With Rheumatoid Arthritis and Inadequate Response to Methotrexate (NCT NCT00578305)
NCT ID: NCT00578305
Last Updated: 2015-04-10
Results Overview
The erosion score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists. Each location was scored in 0.5 increments from 0 to 10 with each integer unit increment representing a 10% loss of articular bone using the following scale. 0.0=normal, no erosion; 0.5=1-5% erosion; 1.0=6-10% erosion; 1.5=11-15% erosion; 2.0=16-20% erosion; etc, up to 10.0=96-100% erosion. The individual scores were summed and normalized to a range of 0 to 100 with a higher score indicating more erosion. A negative change score indicates improvement.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
185 participants
Primary outcome timeframe
Baseline to Week 24
Results posted on
2015-04-10
Participant Flow
Participant milestones
| Measure |
Rituximab 500 mg
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
|---|---|---|---|
|
Double-blind Treatment Phase
STARTED
|
62
|
60
|
63
|
|
Double-blind Treatment Phase
Treated
|
62
|
60
|
63
|
|
Double-blind Treatment Phase
COMPLETED
|
59
|
56
|
49
|
|
Double-blind Treatment Phase
NOT COMPLETED
|
3
|
4
|
14
|
|
Extension Phase
STARTED
|
53
|
50
|
43
|
|
Extension Phase
COMPLETED
|
49
|
49
|
40
|
|
Extension Phase
NOT COMPLETED
|
4
|
1
|
3
|
|
Safety Follow-up Phase
STARTED
|
57
|
54
|
54
|
|
Safety Follow-up Phase
COMPLETED
|
11
|
9
|
8
|
|
Safety Follow-up Phase
NOT COMPLETED
|
46
|
45
|
46
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of Rituximab (MabThera®/Rituxan®) in Patients With Rheumatoid Arthritis and Inadequate Response to Methotrexate
Baseline characteristics by cohort
| Measure |
Rituximab 500 mg
n=62 Participants
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg
n=60 Participants
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo
n=63 Participants
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Total
n=185 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
48.7 years
STANDARD_DEVIATION 11.10 • n=93 Participants
|
50.7 years
STANDARD_DEVIATION 11.65 • n=4 Participants
|
50.3 years
STANDARD_DEVIATION 11.94 • n=27 Participants
|
49.9 years
STANDARD_DEVIATION 11.54 • n=483 Participants
|
|
Sex: Female, Male
Female
|
45 Participants
n=93 Participants
|
50 Participants
n=4 Participants
|
48 Participants
n=27 Participants
|
143 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=93 Participants
|
10 Participants
n=4 Participants
|
15 Participants
n=27 Participants
|
42 Participants
n=483 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 24Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
The erosion score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists. Each location was scored in 0.5 increments from 0 to 10 with each integer unit increment representing a 10% loss of articular bone using the following scale. 0.0=normal, no erosion; 0.5=1-5% erosion; 1.0=6-10% erosion; 1.5=11-15% erosion; 2.0=16-20% erosion; etc, up to 10.0=96-100% erosion. The individual scores were summed and normalized to a range of 0 to 100 with a higher score indicating more erosion. A negative change score indicates improvement.
Outcome measures
| Measure |
Rituximab 500 mg
n=59 Participants
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg
n=58 Participants
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo
n=60 Participants
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
|---|---|---|---|
|
Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Week 24
|
0.13 Units on a scale
Standard Deviation 2.258
|
0.39 Units on a scale
Standard Deviation 1.807
|
1.33 Units on a scale
Standard Deviation 2.235
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
The erosion score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists. Each location was scored in 0.5 increments from 0 to 10 with each integer unit increment representing a 10% loss of articular bone using the following scale. 0.0=normal, no erosion; 0.5=1-5% erosion; 1.0=6-10% erosion; 1.5=11-15% erosion; 2.0=16-20% erosion; etc, up to 10.0=96-100% erosion. The individual scores were summed and normalized to a range of 0 to 100 with a higher score indicating more erosion. A negative change score indicates improvement.
Outcome measures
| Measure |
Rituximab 500 mg
n=60 Participants
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg
n=62 Participants
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo
n=63 Participants
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
|---|---|---|---|
|
Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Weeks 12 and 52
Week 12 (n = 58, 58, 56)
|
0.42 Units on a scale
Standard Deviation 1.693
|
0.13 Units on a scale
Standard Deviation 1.764
|
0.33 Units on a scale
Standard Deviation 4.122
|
|
Change in Magnetic Resonance Imaging (MRI) Erosion Score From Baseline to Weeks 12 and 52
Week 52 (n = 56, 57, 58)
|
0.11 Units on a scale
Standard Deviation 2.623
|
-0.30 Units on a scale
Standard Deviation 2.372
|
3.02 Units on a scale
Standard Deviation 4.456
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
The synovitis score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images of 3 wrist regions and 5 metacarpophalangeal joints in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists. Each location was scored in 0.5 increments from 0 to 3 with each integer unit increment representing a 33% enhancement of the maximum volume of enhancing tissue in the synovial compartment using the following scale: 0.0=normal, no synovitis; 0.5=1-17% estimated volume of enhancement; 1.0=18-33%; 1.5=34-50%; 2.0=51-67%; 2.5=68-83%; 3.0=84-100% estimated volume of enhancement. The individual scores were summed and normalized to a range of 0 to 100 with a higher score indicating more synovitis. A negative change score indicates improvement.
Outcome measures
| Measure |
Rituximab 500 mg
n=62 Participants
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg
n=60 Participants
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo
n=63 Participants
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
|---|---|---|---|
|
Change in Magnetic Resonance Imaging (MRI) Synovitis Score From Baseline to Weeks 12, 24, and Week 52
Week 24 (n = 61, 59, 59)
|
-1.14 Units on a scale
Standard Deviation 1.923
|
-1.81 Units on a scale
Standard Deviation 2.289
|
0.20 Units on a scale
Standard Deviation 2.257
|
|
Change in Magnetic Resonance Imaging (MRI) Synovitis Score From Baseline to Weeks 12, 24, and Week 52
Week 12 (n = 58, 58, 56)
|
-0.50 Units on a scale
Standard Deviation 1.701
|
-1.15 Units on a scale
Standard Deviation 1.866
|
-0.22 Units on a scale
Standard Deviation 2.050
|
|
Change in Magnetic Resonance Imaging (MRI) Synovitis Score From Baseline to Weeks 12, 24, and Week 52
Week 52 (n = 61, 59, 59)
|
-2.03 Units on a scale
Standard Deviation 2.562
|
-2.73 Units on a scale
Standard Deviation 3.120
|
-0.01 Units on a scale
Standard Deviation 2.700
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
The osteitis score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Each location was scored in 0.5 increments from 0 to 3 with each integer unit increment representing a 33% increase in the volume of the peripheral 1 cm of original (eroded + residual) articular bone using the following scale: 0.0=normal, no osteitis; 0.5=1-17% involvement of original articular bone; 1.0=18-33%; 1.5=34-50%; 2.0=51-67%; 2.5=68-83%; 3.0=84-100% involvement of original articular bone. The individual scores were summed and normalized to a range of 0 to 100 with a higher score indicating more synovitis. A negative change score indicates improvement.
Outcome measures
| Measure |
Rituximab 500 mg
n=62 Participants
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg
n=60 Participants
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo
n=63 Participants
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
|---|---|---|---|
|
Change in Magnetic Resonance Imaging (MRI) Osteitis Score From Baseline to Weeks 12, 24, and Week 52
Week 24 (n = 61, 59, 59)
|
-2.91 Units on a scale
Standard Deviation 5.687
|
-2.86 Units on a scale
Standard Deviation 5.976
|
0.07 Units on a scale
Standard Deviation 5.574
|
|
Change in Magnetic Resonance Imaging (MRI) Osteitis Score From Baseline to Weeks 12, 24, and Week 52
Week 12 (n = 58, 58, 56)
|
-2.11 Units on a scale
Standard Deviation 5.049
|
-1.88 Units on a scale
Standard Deviation 5.366
|
-0.14 Units on a scale
Standard Deviation 3.940
|
|
Change in Magnetic Resonance Imaging (MRI) Osteitis Score From Baseline to Weeks 12, 24, and Week 52
Week 52 (n = 61, 59, 59)
|
-4.75 Units on a scale
Standard Deviation 7.413
|
-3.83 Units on a scale
Standard Deviation 6.255
|
-0.22 Units on a scale
Standard Deviation 6.390
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
No newly eroded joints was defined as no new erosions in joints which were scored 0 at baseline. The erosion score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists. Each location was scored in 0.5 increments from 0 to 10 with each integer unit increment representing a 10% loss of articular bone using the following scale. 0.0=normal, no erosion; 0.5=1-5% erosion; 1.0=6-10% erosion; 1.5=11-15% erosion; 2.0=16-20% erosion; etc, up to 10.0=96-100% erosion.
Outcome measures
| Measure |
Rituximab 500 mg
n=62 Participants
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg
n=60 Participants
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo
n=63 Participants
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
|---|---|---|---|
|
Percentage of Participants With no Newly Eroded Joints at Weeks 24 and 52
Week 24
|
77.4 Percentage of participants
|
73.3 Percentage of participants
|
55.5 Percentage of participants
|
|
Percentage of Participants With no Newly Eroded Joints at Weeks 24 and 52
Week 52
|
77.4 Percentage of participants
|
40 Percentage of participants
|
60.3 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
There were 2 definitions of no progression/no worsening in bone erosion. A participant met the criterion for definition 1 when there was a change in the magnetic resonance imaging erosion score ≤ 0. A participant met the criteria for definition 2 when there was either (1) no change from Baseline in the MRI erosion score, (2) an increase in erosion score and the size of the increase in score was smaller than the smallest detectable change, or (3) a drop in the erosion score. The erosion score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring (RAMRIS) system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists.
Outcome measures
| Measure |
Rituximab 500 mg
n=62 Participants
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg
n=60 Participants
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo
n=63 Participants
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
|---|---|---|---|
|
Percentage of Participants With no Progression/no Worsening in Bone Erosion at Weeks 24 and 52
Week 24 (Definition 2)
|
88.7 Percentage of participants
|
96.7 Percentage of participants
|
81.0 Percentage of participants
|
|
Percentage of Participants With no Progression/no Worsening in Bone Erosion at Weeks 24 and 52
Week 24 (Definition 1)
|
50.0 Percentage of participants
|
51.7 Percentage of participants
|
33.3 Percentage of participants
|
|
Percentage of Participants With no Progression/no Worsening in Bone Erosion at Weeks 24 and 52
Week 52 (Definition 1)
|
48.4 Percentage of participants
|
55.0 Percentage of participants
|
27.0 Percentage of participants
|
|
Percentage of Participants With no Progression/no Worsening in Bone Erosion at Weeks 24 and 52
Week 52 (Definition 2)
|
85.5 Percentage of participants
|
93.3 Percentage of participants
|
55.6 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
There were 2 definitions of improvement in synovitis. A participant met the criterion for definition 1 when there was a drop in the magnetic resonance imaging synovitis score from Baseline \> 0.5. A participant met the criterion for definition 2 when there was a drop in the magnetic resonance imaging synovitis score from Baseline \> than the smallest detectable change. The synovitis score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI (RAMRIS) scoring system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists.
Outcome measures
| Measure |
Rituximab 500 mg
n=62 Participants
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg
n=60 Participants
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo
n=63 Participants
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
|---|---|---|---|
|
Percentage of Participants With Improvement in Synovitis at Weeks 24 and 52
Week 24 (Definition 1)
|
41.9 Percentage of participants
|
56.7 Percentage of participants
|
22.2 Percentage of participants
|
|
Percentage of Participants With Improvement in Synovitis at Weeks 24 and 52
Week 24 (Definition 2)
|
41.9 Percentage of participants
|
56.7 Percentage of participants
|
22.2 Percentage of participants
|
|
Percentage of Participants With Improvement in Synovitis at Weeks 24 and 52
Week 52 (Definition 1)
|
54.8 Percentage of participants
|
60.0 Percentage of participants
|
25.4 Percentage of participants
|
|
Percentage of Participants With Improvement in Synovitis at Weeks 24 and 52
Week 52 (Definition 2)
|
54.8 Percentage of participants
|
60.0 Percentage of participants
|
25.4 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
There were 2 definitions of improvement in osteitis. A participant met the criterion for definition 1 when there was a drop in the magnetic resonance imaging osteitis score from Baseline \> 0.5. A participant met the criterion for definition 2 when there was a drop in the magnetic resonance imaging osteitis score from Baseline \> than the smallest detectable change. The osteitis score was determined according to the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI (RAMRIS) scoring system in magnetic resonance images with and without gadolinium of 15 anatomical locations in each wrist and 10 locations in each hand in the hand and wrist with the most arthritic activity. If there was no difference in disease activity between the hands, the dominant hand was used. Images were assessed by 2 experienced blinded musculoskeletal radiologists.
Outcome measures
| Measure |
Rituximab 500 mg
n=62 Participants
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg
n=60 Participants
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo
n=63 Participants
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
|---|---|---|---|
|
Percentage of Participants With Improvement in Osteitis at Weeks 24 and 52
Week 52 (Definition 1)
|
58.1 Percentage of participants
|
51.7 Percentage of participants
|
27.0 Percentage of participants
|
|
Percentage of Participants With Improvement in Osteitis at Weeks 24 and 52
Week 24 (Definition 1)
|
50.0 Percentage of participants
|
51.7 Percentage of participants
|
22.2 Percentage of participants
|
|
Percentage of Participants With Improvement in Osteitis at Weeks 24 and 52
Week 24 (Definition 2)
|
50.0 Percentage of participants
|
51.7 Percentage of participants
|
22.2 Percentage of participants
|
|
Percentage of Participants With Improvement in Osteitis at Weeks 24 and 52
Week 52 (Definition 2)
|
58.1 Percentage of participants
|
51.7 Percentage of participants
|
27.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, C-reactive protein level (CRP), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(CRO)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints, GH = a participant's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A negative change score indicates improvement.
Outcome measures
| Measure |
Rituximab 500 mg
n=62 Participants
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg
n=60 Participants
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo
n=63 Participants
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
|---|---|---|---|
|
Change From Baseline in the Disease Activity Score 28 (DAS28) at Weeks 24 and 52
Week 24 (n = 63, 62, 59)
|
-1.714 Units on a scale
Standard Deviation 1.2204
|
-1.683 Units on a scale
Standard Deviation 1.0158
|
-0.752 Units on a scale
Standard Deviation 1.1834
|
|
Change From Baseline in the Disease Activity Score 28 (DAS28) at Weeks 24 and 52
Week 52 (n = 63, 62, 59)
|
-2.055 Units on a scale
Standard Deviation 1.1844
|
-1.801 Units on a scale
Standard Deviation 1.0443
|
-0.747 Units on a scale
Standard Deviation 1.2557
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
Change of the DAS28 score from Baseline was used to determine the EULAR responses. For a post-Baseline score ≤ 3.2, a change from Baseline of \< -1.2 was a good response, \< -0.6 to ≥ -1.2 was a moderate response, and ≥ -0.6 was no response. For a post-Baseline score \> 3.2 to ≤ 5.1, a change from Baseline of \< -0.6 was a moderate response and ≥ -0.6 was no response. For a post-Baseline score \> 5.1, a change from Baseline \< -1.2 was a moderate response and ≥ -1.2 was no response. A good response could not be achieved for post-Baseline scores \> 3.2. DAS28=(0.56×√(TJC28))+(0.28×√(SJC28))+(0.7×log(CRP))+(0.014×GH), where TJC28=tender joint count (JC) and SJC28=swollen JC (28 joints), GH=a participant's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end=no disease activity, right end=maximum disease activity), and CRP=C-reactive protein level. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Outcome measures
| Measure |
Rituximab 500 mg
n=62 Participants
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg
n=60 Participants
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo
n=63 Participants
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
|---|---|---|---|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52
Week 24 - No response
|
33.9 Percentage of participants
|
22.0 Percentage of participants
|
58.7 Percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52
Week 24 - Moderate response
|
37.1 Percentage of participants
|
42.4 Percentage of participants
|
22.2 Percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52
Week 24 - Good response
|
29.0 Percentage of participants
|
35.6 Percentage of participants
|
19.0 Percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52
Week 52 (n = 63, 62, 59) - No response
|
21.0 Percentage of participants
|
13.6 Percentage of participants
|
60.3 Percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52
Week 52 (n = 63, 62, 59) - Moderate response
|
45.2 Percentage of participants
|
49.2 Percentage of participants
|
31.7 Percentage of participants
|
|
Percentage of Participants With European League Against Rheumatism (EULAR) Good, Moderate, or no Response at Weeks 24 and 52
Week 52 (n = 63, 62, 59) - Good response
|
33.9 Percentage of participants
|
37.3 Percentage of participants
|
7.9 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
The percentage of participants who had low rheumatic arthritis disease activity at Weeks 24 and 52, as measured by a DAS28 score ≤ 3.2, is reported. DAS28 is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(CRO)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints, GH = a participant's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]), and CRP = C-reactive protein level. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Outcome measures
| Measure |
Rituximab 500 mg
n=62 Participants
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg
n=60 Participants
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo
n=63 Participants
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
|---|---|---|---|
|
Percentage of Participants With Low Disease Activity (Disease Activity Score 28 [DAS28] ≤ 3.2) at Weeks 24 and 52
Week 24
|
33.9 Percentage of participants
|
36.7 Percentage of participants
|
19.0 Percentage of participants
|
|
Percentage of Participants With Low Disease Activity (Disease Activity Score 28 [DAS28] ≤ 3.2) at Weeks 24 and 52
Week 52
|
37.1 Percentage of participants
|
38.3 Percentage of participants
|
9.5 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
The percentage of participants in remission of their rheumatic arthritis at Weeks 24 and 52, as measured by a DAS28 score \< 2.6, is reported. DAS28 is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(CRO)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints, GH = a participant's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity \[symptom-free and no arthritis symptoms\], right end = maximum disease activity \[maximum arthritis disease activity\]), and CRP = C-reactive protein level. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.
Outcome measures
| Measure |
Rituximab 500 mg
n=62 Participants
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg
n=60 Participants
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo
n=63 Participants
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
|---|---|---|---|
|
Percentage of Participants in Remission Response (Disease Activity Score 28 [DAS28] < 2.6) at Weeks 24 and 52
Week 24
|
21.0 Percentage of participants
|
28.3 Percentage of participants
|
12.7 Percentage of participants
|
|
Percentage of Participants in Remission Response (Disease Activity Score 28 [DAS28] < 2.6) at Weeks 24 and 52
Week 52
|
25.8 Percentage of participants
|
25.0 Percentage of participants
|
7.9 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
Improvement must be seen in tender and swollen joint counts (28 assessed joints; Joints were evaluated and classified as swollen or not swollen and tender or not tender based on pressure and joint manipulation upon physical examination) and in at least 3
Outcome measures
| Measure |
Rituximab 500 mg
n=62 Participants
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg
n=60 Participants
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo
n=63 Participants
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
|---|---|---|---|
|
Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52
Week 52 - ACR50 response
|
37.1 Percentage of participants
|
35.0 Percentage of participants
|
14.3 Percentage of participants
|
|
Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52
Week 24 - ACR20 response
|
51.6 Percentage of participants
|
51.7 Percentage of participants
|
28.6 Percentage of participants
|
|
Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52
Week 24 - ACR50 response
|
24.2 Percentage of participants
|
26.7 Percentage of participants
|
11.1 Percentage of participants
|
|
Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52
Week 24 - ACR70 response
|
11.3 Percentage of participants
|
8.3 Percentage of participants
|
1.6 Percentage of participants
|
|
Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52
Week 52 - ACR20 response
|
67.7 Percentage of participants
|
68.3 Percentage of participants
|
28.6 Percentage of participants
|
|
Percentage of Participants With an Improvement of at Least 20%, 50%, or 70% in the American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Weeks 24 and 52
Week 52 - ACR70 response
|
17.7 Percentage of participants
|
16.7 Percentage of participants
|
6.3 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
A major clinical response was defined as an improvement of at least 70% in the American College of Rheumatology score from Baseline at Week 52. Improvement must be seen in tender and swollen joint counts (28 assessed joints) and in at least 3 of the following 5 parameters: Separate participant and physician assessments of participant disease activity in the previous 24 hours on a visual analog scale (VAS, the extreme left end of the line "no disease activity" \[symptom-free and no arthritis symptoms\] and the extreme right end "maximum disease activity"); participant assessment of pain in previous the 24 hours on a VAS (extreme left end of the line "no pain" and the extreme right end "unbearable pain"); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C reactive protein level.
Outcome measures
| Measure |
Rituximab 500 mg
n=62 Participants
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg
n=60 Participants
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo
n=63 Participants
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
|---|---|---|---|
|
Percentage of Participants Achieving a Major Clinical Response at Week 52
|
6.5 Percentage of participants
|
6.7 Percentage of participants
|
1.6 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
Correlation coefficients of magnetic resonance imaging erosion, synovitis, and osteitis scores and clinical outcome measures of swollen joint count (SJC), tender joint count (TJC), C-reactive protein level (CRP), erythrocyte sedimentation rate (ESR), a participant's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (GH), Disease Activity Score 28-C-reactive protein (DAS28-CRP), and Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) are reported. Not all of these variables were specified as primary or secondary Outcome Measures in the study protocol and were not individually analyzed.
Outcome measures
| Measure |
Rituximab 500 mg
n=62 Participants
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg
n=60 Participants
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo
n=63 Participants
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
|---|---|---|---|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Synovitis score and TJC - Week 24
|
0.336 Correlation coefficient
|
0.174 Correlation coefficient
|
0.282 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Osteitis score and TJC - Week 24
|
0.355 Correlation coefficient
|
0.118 Correlation coefficient
|
0.288 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Osteitis score and TJC - Week 52
|
0.245 Correlation coefficient
|
0.048 Correlation coefficient
|
0.371 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Erosion score and CRP - Week 24
|
0.185 Correlation coefficient
|
-0.024 Correlation coefficient
|
0.006 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Erosion score and ESR - Week 24
|
0.321 Correlation coefficient
|
0.136 Correlation coefficient
|
0.197 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Erosion score and GH - Week 52
|
0.063 Correlation coefficient
|
-0.009 Correlation coefficient
|
0.316 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Erosion score and DAS28-CRP - Week 24
|
0.420 Correlation coefficient
|
0.198 Correlation coefficient
|
0.457 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Synovitis score and DAS28-CRP - Week 52
|
0.149 Correlation coefficient
|
0.150 Correlation coefficient
|
0.500 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Erosion score and DAS28-ESR - Week 52
|
0.244 Correlation coefficient
|
0.180 Correlation coefficient
|
0.473 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Synovitis score and DAS28-ESR - Week 24
|
0.398 Correlation coefficient
|
0.332 Correlation coefficient
|
0.438 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Osteitis score and DAS28-ESR - Week 52
|
0.108 Correlation coefficient
|
0.172 Correlation coefficient
|
0.356 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Erosion score and SJC - Week 24
|
0.341 Correlation coefficient
|
0.425 Correlation coefficient
|
0.446 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Erosion score and SJC - Week 52
|
0.287 Correlation coefficient
|
0.234 Correlation coefficient
|
0.355 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Synovitis score and SJC - Week 24
|
0.329 Correlation coefficient
|
0.389 Correlation coefficient
|
0.566 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Synovitis score and SJC - Week 52
|
0.168 Correlation coefficient
|
0.188 Correlation coefficient
|
0.574 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Osteitis score and SJC - Week 24
|
0.407 Correlation coefficient
|
0.354 Correlation coefficient
|
0.370 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Osteitis score and SJC - Week 52
|
0.265 Correlation coefficient
|
0.192 Correlation coefficient
|
0.398 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Erosion score and TJC - Week 24
|
0.364 Correlation coefficient
|
0.115 Correlation coefficient
|
0.298 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Erosion score and TJC - Week 52
|
0.275 Correlation coefficient
|
0.067 Correlation coefficient
|
0.425 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Synovitis score and TJC - Week 52
|
0.142 Correlation coefficient
|
0.036 Correlation coefficient
|
0.421 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Erosion score and CRP - Week 52
|
0.055 Correlation coefficient
|
0.098 Correlation coefficient
|
0.352 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Synovitis score and CRP - Week 24
|
0.030 Correlation coefficient
|
0.090 Correlation coefficient
|
0.192 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Synovitis score and CRP - Week 52
|
-0.077 Correlation coefficient
|
0.085 Correlation coefficient
|
0.311 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Osteitis score and CRP - Week 24
|
-0.031 Correlation coefficient
|
-0.057 Correlation coefficient
|
0.040 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Osteitis score and CRP - Week 52
|
0.005 Correlation coefficient
|
-0.010 Correlation coefficient
|
0.119 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Erosion score and ESR - Week 52
|
0.127 Correlation coefficient
|
0.188 Correlation coefficient
|
0.314 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Synovitis score and ESR - Week 24
|
0.182 Correlation coefficient
|
0.214 Correlation coefficient
|
0.358 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Synovitis score and ESR - Week 52
|
0.185 Correlation coefficient
|
0.248 Correlation coefficient
|
0.360 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Osteitis score and ESR - Week 24
|
0.044 Correlation coefficient
|
0.043 Correlation coefficient
|
0.148 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Osteitis score and ESR - Week 52
|
-0.041 Correlation coefficient
|
0.116 Correlation coefficient
|
0.205 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Erosion score and GH - Week 24
|
0.206 Correlation coefficient
|
0.043 Correlation coefficient
|
0.326 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Synovitis score and GH - Week 24
|
0.186 Correlation coefficient
|
0.221 Correlation coefficient
|
0.206 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Synovitis score and GH - Week 52
|
-0.026 Correlation coefficient
|
-0.037 Correlation coefficient
|
0.286 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Osteitis score and GH - Week 24
|
0.274 Correlation coefficient
|
0.122 Correlation coefficient
|
0.205 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Osteitis score and GH - Week 52
|
0.106 Correlation coefficient
|
0.052 Correlation coefficient
|
0.136 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Erosion score and DAS28-CRP - Week 52
|
0.238 Correlation coefficient
|
0.127 Correlation coefficient
|
0.498 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Synovitis score and DAS28-CRP - Week 24
|
0.393 Correlation coefficient
|
0.349 Correlation coefficient
|
0.437 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Osteitis score and DAS28-CRP - Week 24
|
0.380 Correlation coefficient
|
0.209 Correlation coefficient
|
0.351 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Osteitis score and DAS28-CRP - Week 52
|
0.139 Correlation coefficient
|
0.143 Correlation coefficient
|
0.356 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Erosion score and DAS28-ESR - Week 24
|
0.429 Correlation coefficient
|
0.255 Correlation coefficient
|
0.439 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Synovitis score and DAS28-ESR - Week 52
|
0.198 Correlation coefficient
|
0.147 Correlation coefficient
|
0.514 Correlation coefficient
|
|
Correlation of Magnetic Resonance Imaging Assessments and Clinical Outcome Measures
Osteitis score and DAS28-ESR - Week 24
|
0.353 Correlation coefficient
|
0.231 Correlation coefficient
|
0.353 Correlation coefficient
|
SECONDARY outcome
Timeframe: Baseline to Week 52Population: Intent-to-treat population: All randomized participants and received any part of an infusion of study medication during the main study.
The HAQ-DI assesses how well the patient is able to perform 8 activities: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. The patient answers 20 questions with 1 of 4 responses with the past week as the time frame: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. The highest score for any question in a category determines the category score. The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement.
Outcome measures
| Measure |
Rituximab 500 mg
n=62 Participants
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg
n=60 Participants
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo
n=63 Participants
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
|---|---|---|---|
|
Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 24 and 52
Week 52 (n = 63, 62, 59)
|
-0.520 Units on a scale
Standard Deviation 0.5873
|
-0.417 Units on a scale
Standard Deviation 0.4450
|
-0.177 Units on a scale
Standard Deviation 0.5943
|
|
Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 24 and 52
Week 24 (n = 63, 62, 59)
|
-0.425 Units on a scale
Standard Deviation 0.5606
|
-0.439 Units on a scale
Standard Deviation 0.4770
|
-0.194 Units on a scale
Standard Deviation 0.5849
|
SECONDARY outcome
Timeframe: Throughout studyOutcome measures
Outcome data not reported
Adverse Events
Rituximab 500 mg - Double-blind Treatment Phase
Serious events: 3 serious events
Other events: 24 other events
Deaths: 0 deaths
Rituximab 1000 mg - Double-blind Treatment Phase
Serious events: 4 serious events
Other events: 24 other events
Deaths: 0 deaths
Placebo - Double-blind Treatment Phase
Serious events: 5 serious events
Other events: 20 other events
Deaths: 0 deaths
Rituximab 500 mg - Extension Phase
Serious events: 3 serious events
Other events: 0 other events
Deaths: 0 deaths
Rituximab 1000 mg - Extension Phase
Serious events: 5 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo - Extension Phase
Serious events: 2 serious events
Other events: 0 other events
Deaths: 0 deaths
Rituximab 500 mg - Safety Follow-up Phase
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Rituximab 1000 mg - Safety Follow-up Phase
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo - Safety Follow-up Phase
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Rituximab 500 mg - Double-blind Treatment Phase
n=62 participants at risk
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg - Double-blind Treatment Phase
n=60 participants at risk
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo - Double-blind Treatment Phase
n=63 participants at risk
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 500 mg - Extension Phase
n=50 participants at risk
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg - Extension Phase
n=47 participants at risk
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo - Extension Phase
n=41 participants at risk
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 500 mg - Safety Follow-up Phase
n=57 participants at risk
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg - Safety Follow-up Phase
n=54 participants at risk
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo - Safety Follow-up Phase
n=54 participants at risk
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
|---|---|---|---|---|---|---|---|---|---|
|
Infections and infestations
Bronchitis
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
1.7%
1/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Infections and infestations
Omphalitis
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
1.7%
1/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Infections and infestations
Soft tissue infection
|
1.6%
1/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
3.2%
2/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Cardiac disorders
Acute coronary syndrome
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
1.6%
1/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Gastrointestinal disorders
Colonic polyp
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
1.6%
1/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Gastrointestinal disorders
Intestinal diverticulum
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
1.6%
1/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
General disorders
General physical health deterioration
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
1.6%
1/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
1.6%
1/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary serous endometrial carcinoma
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
1.7%
1/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Pregnancy, puerperium and perinatal conditions
Omphalorrhexis
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
1.7%
1/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Renal and urinary disorders
Renal colic
|
1.6%
1/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis chronic
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
1.7%
1/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Infections and infestations
Appendicitis
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
2.0%
1/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Infections and infestations
Erysipelas
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
2.4%
1/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Infections and infestations
Respiratory tract infection viral
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
2.1%
1/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
2.1%
1/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Musculoskeletal and connective tissue disorders
Knee deformity
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
2.1%
1/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colorectal cancer
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
2.1%
1/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
2.1%
1/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
2.0%
1/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
2.4%
1/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
2.4%
1/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Nervous system disorders
Lumbar radiculopathy
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
2.0%
1/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Reproductive system and breast disorders
Breast mass
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
2.1%
1/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma Stage 0
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
1.9%
1/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
Other adverse events
| Measure |
Rituximab 500 mg - Double-blind Treatment Phase
n=62 participants at risk
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg - Double-blind Treatment Phase
n=60 participants at risk
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo - Double-blind Treatment Phase
n=63 participants at risk
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 500 mg - Extension Phase
n=50 participants at risk
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg - Extension Phase
n=47 participants at risk
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo - Extension Phase
n=41 participants at risk
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 500 mg - Safety Follow-up Phase
n=57 participants at risk
Participants received rituximab 500 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Rituximab 1000 mg - Safety Follow-up Phase
n=54 participants at risk
Participants received rituximab 1000 mg iv on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants received further treatment courses on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
Placebo - Safety Follow-up Phase
n=54 participants at risk
Participants received placebo intravenously (iv) on Day 1 and Day 15 of the main study. Participants received a second course of treatment on Day 1 and Day 15 after Week 24 of the main study, if they met eligibility criteria (see the Detailed Description). Participants were switched to receive rituximab 1000 mg iv on Day 1 and Day 15 at intervals of ≥ 6 months after Week 52 in the study extension phase, if they met eligibility criteria (see the Detailed Description). Throughout the study, participants received methylprednisolone 100 mg iv prior to infusion of the investigational drug, methotrexate 7.5 to 25 mg/week orally or parenterally, and folic acid or folate ≥ 5 mg/week orally.
|
|---|---|---|---|---|---|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.5%
4/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
1.6%
1/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.6%
1/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
6.7%
4/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
1.6%
1/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Infections and infestations
Bronchitis
|
6.5%
4/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
8.3%
5/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
3.2%
2/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Nervous system disorders
Headache
|
6.5%
4/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
1.6%
1/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Vascular disorders
Hypertension
|
0.00%
0/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
1.7%
1/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
6.3%
4/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Respiratory, thoracic and mediastinal disorders
Nasopharyngitis
|
3.2%
2/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
5.0%
3/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
3.2%
2/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Infections and infestations
Oral herpes
|
1.6%
1/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
5.0%
3/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Immune system disorders
Rheumatoid arthritis
|
3.2%
2/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
1.7%
1/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
9.5%
6/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection
|
3.2%
2/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
6.7%
4/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
1.6%
1/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
|
Infections and infestations
Viral infection
|
6.5%
4/62
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
5.0%
3/60
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
3.2%
2/63
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/50
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/47
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/41
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/57
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
0.00%
0/54
Safety population: All participants who received any part of an infusion of the study drug during the main study. Some participants entered the safety follow-up period directly from the double-blind treatment period.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER