Rituximab for rheumatoid arthritis refractory to anti–tumor necrosis factor therapy: Results of a multicenter, randomized, double‐blind, placebo‐controlled, phase III trial evaluating primary efficacy and safety at twenty‐four weeks

作者：Stanley B. Cohen, Paul E. Emery, Maria Greenwald, Maxime Dougados, Richard Alan Furie, Mark C. Genovese, Edward Clark Keystone, J. Loveless, Gerd‐Rüdiger Burmester, Matthew W. Cravets, Eva W. Hessey, T Shaw, Mark C. Totoritis · 发表于：Arthritis & Rheumatism · 年份：2006 · DOI：10.1002/art.22025 · 被引用次数：1650 · 研究领域：Rheumatoid Arthritis Research and Therapies、Spondyloarthritis Studies and Treatments、Autoimmune and Inflammatory Disorders Research

OBJECTIVE: To determine the efficacy and safety of treatment with rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to anti-tumor necrosis factor (anti-TNF) therapies and to explore the pharmacokinetics and pharmacodynamics of rituximab in this population. METHODS: We evaluated primary efficacy and safety at 24 weeks in patients enrolled in the Randomized Evaluation of Long-Term Efficacy of Rituximab in RA (REFLEX) Trial, a 2-year, multicenter, randomized, double-blind, placebo-controlled, phase III study of rituximab therapy. Patients with active RA and an inadequate response to 1 or more anti-TNF agents were randomized to receive intravenous rituximab (1 course, consisting of 2 infusions of 1,000 mg each) or placebo, both with background MTX. The primary efficacy end point was a response on the American College of Rheumatology 20% improvement criteria (ACR20) at 24 weeks. Secondary end points were responses on the ACR50 and ACR70 improvement criteria, the Disease Activity Score in 28 joints, and the European League against Rheumatism (EULAR) response criteria at 24 weeks. Additional end points included scores on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Health Assessment Questionnaire (HAQ) Disability Index (DI), and Short Form 36 (SF-36) instruments, as well as Genant-modified Sharp radiographic scores at 24 weeks. RESULTS: Patients assigned to placebo (n = 209) and rituximab (n ...