A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate
A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate
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DOI：
10.1056/nejm199901283400401
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发表时间：
1999-01-28
影响因子：
158.5
通讯作者：
Burge, DJ
中科院分区：
文献类型：
--
作者：
Weinblatt, ME;Kremer, JM;Burge, DJ
用甲氨蝶呤治疗类风湿性关节炎的患者病情通常有所改善，但仍有活动性疾病。本研究旨在确定添加依那西普（一种可溶性肿瘤坏死因子受体（p75）：Fc融合蛋白（TNFR：Fc），甲氨蝶呤治疗将提供额外的好处，患者谁有持续性类风湿关节炎，尽管接受甲氨蝶呤。我们随机分配了89名持续活动性类风湿关节炎患者，尽管他们至少接受了6个月的甲氨蝶呤治疗，剂量稳定在每周15 - 25 mg。（或对于不能耐受更高剂量的患者，低至每周10 mg）接受依那西普（25 mg）或安慰剂皮下注射，每周两次，同时继续接受甲氨蝶呤。临床反应的主要措施是美国流变学学会标准的20%改善措施的疾病活动（ACR 20）在24 weeks.Results的依那西普甲氨蝶呤治疗导致快速和持续的改善。在24周时，71%的接受依那西普+甲氨蝶呤的患者和27%的接受安慰剂+甲氨蝶呤的患者符合ACR 20标准（P < 0.001）; 39%的接受依那西普+甲氨蝶呤的患者和3%的接受安慰剂+甲氨蝶呤的患者符合ACR 50标准（改善50%）（P < 0.001）。根据所有疾病活动性指标，接受依那西普联合甲氨蝶呤治疗的患者结局明显更好。与依那西普相关的唯一不良事件是轻微的注射部位反应，没有患者退出研究，因为与依那西普相关的不良事件。结论在持续活动性类风湿关节炎患者中，依那西普和甲氨蝶呤的组合是安全的，耐受性良好，并提供显着更大的临床效益比单独甲氨蝶呤。（N Engl J Med 1999;340：253-9，）（C）1999，马萨诸塞州医学会。
Background Patients treated with methotrexate for rheumatoid arthritis often improve but continue to have active disease. This study was undertaken to determine whether the addition of etanercept, a soluble tumor necrosis factor receptor (p75):Fc fusion protein (TNFR:Fc), to methotrexate therapy would provide additional benefit to patients who had persistent rheumatoid arthritis despite receiving methotrexate.Methods In a 24-week, double-blind trial, we randomly assigned 89 patients with persistently active rheumatoid arthritis despite at least 6 months of methotrexate therapy at a stable dose of 15 to 25 mg per week (or as low as 10 mg per week for patients unable to tolerate higher doses) to receive either etanercept (25 mg) or placebo subcutaneously twice weekly while continuing to receive methotrexate. The primary measure of clinical response was the American College of Rheumatology criteria for a 20 percent improvement in measures of disease activity (ACR 20) at 24 weeks.Results The addition of etanercept to methotrexate therapy resulted in rapid and sustained improvement. At 24 weeks, 71 percent of the patients receiving etanercept plus methotrexate and 27 percent of those receiving placebo plus methotrexate met the ACR 20 criteria (P < 0.001); 39 percent of the patients receiving etanercept plus methotrexate and 3 percent of those receiving placebo plus methotrexate met the ACR 50 criteria (for a 50 percent improvement) (P < 0.001). Patients receiving etanercept plus methotrexate had significantly better outcomes according to all measures of disease activity. The only adverse events associated with etanercept were mild injection-site reactions, and no patient withdrew from the study because of adverse events associated with etanercept.Conclusions In patients with persistently active rheumatoid arthritis, the combination of etanercept and methotrexate was safe and well tolerated and provided significantly greater clinical benefit than methotrexate alone. (N Engl J Med 1999;340:253-9,) (C) 1999, Massachusetts Medical Society.