Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis
Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis
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DOI：
10.1056/nejmoa032534
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发表时间：
2004-06-17
影响因子：
158.5
通讯作者：
Shaw, T
中科院分区：
文献类型：
--
作者：
Edwards, JCW;Szczepanski, L;Shaw, T
背景：一项开放标签研究表明，使用利妥昔单抗选择性消耗B细胞导致类风湿关节炎患者的持续临床改善。为了证实这些观察结果，我们进行了一项随机、双盲、对照研究。方法：我们随机分配了161例尽管接受甲氨蝶呤治疗但仍患有活动性类风湿关节炎的患者接受四种治疗中的一种：口服甲氨蝶呤（每周大于/等于10mg）（对照组）；利妥昔单抗（1000mg，第1天和第15天）；利妥昔单抗加环磷酰胺（750 mg，第3天和第17天）；或者美罗华加甲氨蝶呤。根据美国风湿病学会（ACR）和欧洲抗风湿病联盟（EULAR）的标准定义的反应在第24周（初步分析）和第48周（探索性分析）进行评估。结果：在第24周，根据ACR标准（主要终点），利妥昔单抗-甲氨蝶呤联合治疗（43%，P=0.005）和利妥昔单抗-环磷酰胺联合治疗（41%，P=0.005）的疾病症状改善50%的患者比例显著高于单独使用甲氨蝶呤（13%）。在接受利妥昔单抗治疗的所有组中，根据ACR标准，有20%疾病症状改善的患者比例显著增加（65%至76%对38%，P < = 0.025）或有ular反应的患者比例显著增加（83%至85%对50%，P < = 0.004）。利妥昔单抗-甲氨蝶呤组所有ACR反应维持在第48周。大多数不良事件发生在第一次输注利妥昔单抗时：在24周时，对照组中有1例患者（2.5%）发生严重感染，利妥昔单抗组中有4例患者（3.3%）发生严重感染。外周血免疫球蛋白浓度维持在正常范围内。结论：在接受甲氨蝶呤治疗的活动性类风湿关节炎患者中，单疗程两次输注利妥昔单抗，单独或联合环磷酰胺或持续的甲氨蝶呤，在第24周和第48周均可显著改善疾病症状。
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 (greater/equal 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 lessthan/equal 0.025) or had EULAR responses (83 to 85 percent vs. 50 percent, P lessthan/equal 0.004). All ACR responses were maintained at week 48 in the rituximab-methotrexate group. The majority of adverse events occurred with the first rituximab infusion: at 24 weeks, serious infections occurred in one patient (2.5 percent) in the control group and in four patients (3.3 percent) in the rituximab groups. Peripheral-blood immunoglobulin concentrations remained within normal ranges.Conclusions: In patients with active rheumatoid arthritis despite methotrexate treatment, a single course of two infusions of rituximab, alone or in combination with either cyclophosphamide or continued methotrexate, provided significant improvement in disease symptoms at both weeks 24 and 48.