Efficacy of B-Cell–Targeted Therapy with Rituximab in Patients with Rheumatoid Arthritis

作者：Jonathan Edwards, Leszek Szczepanski, Jacek Szechiński, Anna Filipowicz‐Sosnowska, Paul E. Emery, David R. Close, Randall M. Stevens, Tim Shaw · 发表于：New England Journal of Medicine · 年份：2004 · DOI：10.1056/nejmoa032534 · 被引用次数：2641 · 研究领域：Rheumatoid Arthritis Research and Therapies、Monoclonal and Polyclonal Antibodies Research、T-cell and B-cell Immunology

BACKGROUND: An open-label study indicated that selective depletion of B cells with the use of rituximab led to sustained clinical improvements for patients with rheumatoid arthritis. To confirm these observations, we conducted a randomized, double-blind, controlled study. METHODS: We randomly assigned 161 patients who had active rheumatoid arthritis despite treatment with methotrexate to receive one of four treatments: oral methotrexate (> or =10 mg per week) (control); rituximab (1000 mg on days 1 and 15); rituximab plus cyclophosphamide (750 mg on days 3 and 17); or rituximab plus methotrexate. Responses defined according to the criteria of the American College of Rheumatology (ACR) and the European League against Rheumatism (EULAR) were assessed at week 24 (primary analyses) and week 48 (exploratory analyses). RESULTS: At week 24, the proportion of patients with 50 percent improvement in disease symptoms according to the ACR criteria, the primary end point, was significantly greater with the rituximab-methotrexate combination (43 percent, P=0.005) and the rituximab-cyclophosphamide combination (41 percent, P=0.005) than with methotrexate alone (13 percent). In all groups treated with rituximab, a significantly higher proportion of patients had a 20 percent improvement in disease symptoms according to the ACR criteria (65 to 76 percent vs. 38 percent, P< or =0.025) or had EULAR responses (83 to 85 percent vs. 50 percent, P< or =0.004). All ACR responses were maintained at w...