Phase 3
Completed N=516
A Study to Evaluate the Safety and Efficacy of MabThera (Rituximab) in Combination With Methotrexate (MTX) in Participants With Active Rheumatoid Arthritis Who Failed on Anti-Tumor Necrosis Factor Alpha Therapy
Source: ClinicalTrials.gov NCT00468546 ↗Enrolled (actual)
516
Serious AEs
14.7%
Results posted
Oct 2016
Primary outcomePrimary: Number of Participants With American College of Rheumatology 20 Response at Week 24 — 36; 153 participants
◆ Published Evidence
Highly cited
105citations · ~6 / year
Improvement in patient-reported outcomes in a rituximab trial in patients with severe rheumatoid arthritis refractory to anti-tumor necrosis factor therapy.
Summary
This study will assess the safety and efficacy of rituximab combined with MTX in participants with active rheumatoid arthritis (RA) who have had an inadequate response to anti-Tumor Necrosis (TNF) alpha therapy. The anticipated time in the study is up to 2 years and the target sample size is 500 participants. Eligible participants may receive re-treatment with rituximab under a separate protocol WA17531.
Linked Publications (2)
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Improvement in patient-reported outcomes in a rituximab trial in patients with severe rheumatoid arthritis refractory to anti-tumor necrosis factor therapy.
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Inflammation and autoantibody markers identify rheumatoid arthritis patients with enhanced clinical benefit following rituximab treatment.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With American College of Rheumatology 20 Response at Week 24 |
36; 153 | — |
| SECONDARY Number of Participants With an ACR 50 Response at Week 24 |
11; 80 | — |
| SECONDARY Number of Participants With ACR 70 Response at Week 24 |
3; 37 | — |
| SECONDARY Mean Change From Baseline in Disease Activity Score of 28 Joints at Week 24 |
-0.4; -1.9 | — |
| SECONDARY Percentage of Participants With DAS28 Low Disease Activity and DAS28 Remission at Week 24 |
2; 15; 0; 9 | — |
| SECONDARY Number of Participants With Good, Moderate, or no European League Against Rheumatism Responses at Week 24 |
157; 105; 40; 149; 4; 44 | — |
| SECONDARY Percentage Change From Baseline in the ACR Core Set (SJC, TJC, Patient's and Physician's Global Assessments, Health Assessment Questionnaire, Pain, C-Reactive Protein, and Erythrocyte Sedimentation Rate) Score |
-5.6; -43.0; -7.1; -41.3; 7.2; -41.8 | — |
| SECONDARY Mean Change From Baseline of Short Form 36 Total Scores at Week 24 |
0.9; 5.8; 1.3; 4.7 | — |
| SECONDARY Number of Participants With Categorical Change From Baseline in the Physical Component Scores of SF-36 |
25; 141; 158; 136; 14; 17 | — |
| SECONDARY Number of Participants With Change From Baseline in the Mental Component Scores of SF-36 |
40; 111; 128; 144; 29; 39 | — |
| SECONDARY Mean Change From Baseline in the Genant-modified Sharp Joint Space Narrowing Score, Genant-modified Sharp Total Score, and Erosion Score |
-4.3; -1.2; 2.31; 1.00; 2.82; 1.16 | — |
| SECONDARY Percentage of Participants Without Erosive Progression |
51; 66; 58; 73; 44; 60 | — |
Eligibility Criteria
Inclusion Criteria
- Adult participants 18-80 years of age with active RA for at least 6 months;
- Received treatment for RA on an outpatient basis and experienced an inadequate response or intolerance to treatment with at least 1 anti-TNF alpha therapy (etanercept, infliximab or adalimumab);
- Must have received MTX for a minimum of 12 weeks, with the last 4 weeks, prior to screening at a stable dose;
- Participants with swollen joint count (SJC) and tender joint count (TJC) of at least 8 joints at screening and at randomization;
- Radiographic evidence of at least 1 joint with a definite erosion due to RA;
- Participants of reproductive potential must be using reliable contraceptive methods.
Exclusion Criteria
- Bone or joint surgery within 8 weeks prior to screening or joint surgery planned within 24 weeks of randomization;
- Class IV functional status of RA;
- Previous treatment within 6 months with intravenous gamma globulin, or the Prosorba column;
- Intraarticular or parenteral corticosteroids within 4 weeks prior to screening visit;
- With a live vaccine within 4 weeks prior to randomization;
- Previous treatment with rituximab or other cell-depleting therapies;
- Concurrent treatment with any disease-modifying anti-rheumatic drug (except for MTX) or any anti-TNF alfa factor or other biologic therapy;
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies;
- Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders;
- Known contraindications to receiving rituximab;
- Known active bacterial, viral, fungal, mycobacterial or other infection;
- History of recurrent significant infection or history of recurrent bacterial infections;
- Primary or secondary immunodeficiency (history of, or currently active);
- History of cancer, including solid tumors and hematologic malignancies (except basal cell or squamous cell carcinoma of the skin that have been excised and cured);
- Women who are pregnant or breast-feeding;
- History of alcohol, drug or chemical abuse within 6 months prior to screening;
- Neuropathies and neurovasculopathies which might interfere with pain evaluation;
- Participants with poor peripheral venous access;
- Intolerance or contraindications to oral or intravenous corticosteroids.
Data sourced from ClinicalTrials.gov (NCT00468546) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.