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

• Published in: Journal of rheumatology Vol. 39; no. 12; pp. 2238 - 2246
• Main Authors: KEYSTONE, Edward C, COHEN, Stanley B, EMERY, Paul, KREMER, Joel M, DOUGADOS, Maxime, LOVELESS, James E, CHUNG, Carol, WONG, Pamela, LEHANE, Patricia B, TYRRELL, Helen
• Format: Journal Article
• Language: English
• Published: Toronto, ON Journal of Rheumatology Publishing 01-12-2012
• Subjects: Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Murine-Derived - therapeutic use; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - diagnosis; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - physiopathology; Biological and medical sciences; Disability Evaluation; Diseases of the osteoarticular system; Double-Blind Method; Drug Substitution; Drug Therapy, Combination; Female; Health Status; Humans; Immunomodulators; Inflammatory joint diseases; Joints - drug effects; Joints - pathology; Joints - physiopathology; Male; Medical sciences; Methotrexate - therapeutic use; Middle Aged; Pharmacology. Drug treatments; Rituximab; Surveys and Questionnaires; Treatment Failure; Treatment Outcome; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Antineoplastic agent; Human; BIOLOGICAL THERAPY CD20 ANTIBODY RITUXIMAB; Immunopathology; Multiple; Radiodiagnosis; Toxicity; Diseases of the osteoarticular system; Rheumatology; Anti-TNF; Rituximab; Exploration; Autoimmune disease; Inflammatory joint disease; Monoclonal antibody; Immunomodulator; Radiography; Chronic; Biotherapy; Rheumatoid arthritis; Immunosuppressive agent
• ISSN: 0315-162X; 1499-2752
• DOI: 10.3899/jrheum.120573

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.
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.
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).
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.