Multiple courses of rituximab produce sustained clinical and radiographic efficacy and safety in patients with rheumatoid arthritis and an inadequate response to 1 or more tumor necrosis factor inhibitors: 5-year data from the REFLEX study.

Abstract

OBJECTIVE:

This 5-year observational posthoc analysis of the REFLEX study and its open-label extension assessed clinical efficacy, radiographic response, and safety of rituximab (RTX) in patients with rheumatoid arthritis (RA) who had an inadequate response to tumor necrosis factor (TNF) inhibitors.

METHODS:

Patients in REFLEX were originally randomized to placebo (PBO) + methotrexate (MTX; PBO-randomized) or RTX + MTX (RTX-randomized). PBO-randomized patients were rescued with RTX as appropriate. Patients responding to initial RTX treatment could receive further RTX courses. For clinical efficacy and safety analyses, PBO-randomized patients were re-baselined prior to first RTX treatment and the data were pooled with RTX-randomized patient data. Efficacy outcomes 24 weeks after each course were calculated relative to first RTX pretreatment baseline. Radiographic outcomes were assessed relative to randomization baseline for both PBO-randomized and RTX-randomized groups.

RESULTS:

A total of 480 patients received ≥ 1 RTX course. At 24 weeks, American College of Rheumatology 20/50/70 responses were 62.0%, 30.8%, and 13.0%, respectively at course 1 (n = 400) and 70.3%, 41.8%, and 22.0% at course 5 (n = 91). European League Against Rheumatism good/moderate responses were 77.2% and 84.4% at courses 1 (n = 390) and 5 (n = 90). Rates of adverse events (AE), serious AE, and infections generally remained stable. Rate of progressive joint damage (PJD; change in mean Total Sharp Score) decreased over time in both PBO-randomized (n = 79) and RTX-randomized (n = 105) groups. Mean change from baseline in PJD over 5 years was greater in PBO-randomized versus RTX-randomized patients (5.51 vs 3.21).

CONCLUSION:

RTX re-treatment over 5 years is associated with maintained or improved efficacy, continued inhibition of PJD, and a safety profile consistent with that previously reported. A delay in initiating RTX treatment may result in increased PJD.

• Authors: Edward C Keystone, Stanley B Cohen, Paul Emery, Joel M Kremer, Maxime Dougados, James E Loveless, Carol Chung, Pamela Wong, Patricia B Lehane, Helen Tyrrell
• Journal: The Journal of rheumatology (J Rheumatol) Vol. 39 Issue 12 Pg. 2238-46 (Dec 2012) ISSN: 0315-162X [Print] Canada
• PMID: 23027887 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Murine-Derived
• Antirheumatic Agents
• Tumor Necrosis Factor-alpha
• Rituximab
• Methotrexate

Topics

• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Murine-Derived (therapeutic use)
• Antirheumatic Agents (therapeutic use)
• Arthritis, Rheumatoid (diagnosis, drug therapy, physiopathology)
• Disability Evaluation
• Double-Blind Method
• Drug Substitution
• Drug Therapy, Combination
• Female
• Health Status
• Humans
• Joints (drug effects, pathology, physiopathology)
• Male
• Methotrexate (therapeutic use)
• Middle Aged
• Rituximab
• Surveys and Questionnaires
• Treatment Failure
• Treatment Outcome
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)