Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate - Results of a twenty-four-week, multicenter, randomized, double-blind, placebo-controlled trial
Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate - Results of a twenty-four-week, multicenter, randomized, double-blind, placebo-controlled trial
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DOI：
10.1002/art.10141
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发表时间：
2002-03-01
影响因子：
--
通讯作者：
McCabe, D
中科院分区：
文献类型：
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作者：
Cohen, S;Hurd, E;McCabe, D
客观的。评价阿那白滞素联合甲氨蝶呤（MTX）治疗活动性类风湿关节炎（RA）患者的疗效和安全性。方法。连续 6 个月接受 MTX、稳定剂量大于或等于 3 个月的中重度活动性 RA 患者（病程 > 6 个月但 < 12 年的患者）被随机分为 6 组：安慰剂组或每天单次皮下注射 0.04、0.1、0.4、1.0 或 2.0 mg/kg 阿那白滞素组。主要疗效终点是第 12 周时满足美国风湿病学会 20% 改善标准（达到 ACR20 反应）的受试者比例。结果。该研究共有 419 名患者被随机分配。 6 个治疗组的患者人口统计数据和疾病状况相似。与安慰剂加 MTX 组的 ACR220 反应相比，第 12 周时 5 个主动治疗加 MTX 组的 ACR20 反应表现出统计学显着性 (P = 0.001) 的剂量反应关系。阿那白滞素 1.0 mg/kg（46%；P = 0.001）和 21.0 mg/kg（38%；P = 0.007）剂量组的 ACR20 反应率显着高于安慰剂组（19%）。 24 周时的 ACR20 反应与 12 周时的一致。在接受阿那白滞素治疗的受试者中，在个别 ACR 成分、红细胞沉降率、ACR20 反应的开始时间、ACR20 反应的可持续性和 ACR 反应的强度方面也注意到了类似的改善。阿纳白滞素是安全且耐受性良好的。注射部位反应是最常见的不良事件，这导致 7%（1.0 mg/kg 组）至 10% 组）接受较高剂量的患者提前退出研究。结论。对于持续活动性 RA 患者，阿那白滞素和 MTX 联合用药是安全且耐受性良好的，并且比单用 MTX 提供显着更大的临床益处。
Objective. To evaluate the efficacy and safety of anakinra in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA).Methods. Patients with moderate-to-severe active RA who were receiving MTX for 6 consecutive months, with stable doses for greater than or equal to3 months (those with disease duration of > 6 months but < 12 years,) were randomized into 6 groups: placebo or 0.04, 0.1, 0.4, 1.0, or 2.0 mg/kg of anakinra administered in a single, daily, subcutaneous injection. The primary efficacy end point was the proportion of subjects who met the American College of Rheumatology 20% improvement criteria (attained an ACR20 response) at week 12.Results. A total of 419 patients were randomized in the study. Patient demographics and disease status were similar in the 6 treatment groups. The ACR20 responses at week 12 in the 5 active treatment plus MTX groups demonstrated a statistically significant (P = 0.001) dose-response relationship compared with the ACR220 response in the placebo plus MTX group. The ACR20 response rate in the anakinra 1.0-mg/kg (46%; P = 0.001) and 21.0-mg/kg (38%; P = 0.007) dose groups was significantly greater than that in the placebo group (19%). The ACR20 responses at 24 weeks were consistent with those at 12 weeks. Similar improvements in anakinra-treated subjects were noted in individual ACR components, erythrocyte sedimentation rate, onset of ACR20 response, sustainability of ACR20 response, and magnitude of ACR response. Anakinra was safe and well tolerated. Injection site reaction was the most frequently noted adverse event, and this led to premature study withdrawal in 7% (1.0-mg/kg group) to 10% group) of patients receiving higher doses.Conclusion. In patients with persistently active RA, the combination of anakinra and MTX was safe and well tolerated and provided significantly greater clinical benefit than MTX alone.