Nuki George, Bresnihan Barry, Bear Moraye B, McCabe Dorothy
University of Edinburgh, Edinburgh, Scotland, UK.
Arthritis Rheum. 2002 Nov;46(11):2838-46. doi: 10.1002/art.10578.
To demonstrate the long-term efficacy of anakinra, a human recombinant interleukin-1 receptor antagonist, in patients with rheumatoid arthritis (RA), and to assess the long-term safety of anakinra at different daily doses.
The efficacy and safety of anakinra were previously demonstrated in a double-blind, placebo-controlled, 24-week evaluation in 472 patients with active RA. Of 345 patients who completed the placebo-controlled phase of the study, 309 continued in a 52-week, multicenter, double-blind, parallel-group extension phase of the study. Patients received subcutaneous injections of anakinra (30, 75, or 150 mg) once daily. Efficacy was assessed among the 309 patients for the first 24 weeks of the extension phase (48 weeks total therapy), using the American College of Rheumatology composite score (ACR20), its components, and radiographs of the hands and wrists. Safety was assessed in all 472 patients over the entire 52-week extension phase (76 weeks total exposure).
A total of 218 patients completed the extension phase. Of the 91 patients who withdrew prematurely, 46 did so following adverse events, and 26 withdrew because of lack of efficacy. Among patients receiving anakinra who entered the extension phase, the level of improvement was maintained for 48 weeks. The ACR20 response was 51% at week 24 and 46% at week 48, and this effect was consistent across all dose groups. The durability of the response to anakinra was further demonstrated in an evaluation of the sustained ACR20 response, which was similar during the first and second 24-week periods (36% and 42%, respectively). At week 48, ACR50 and ACR70 responses were demonstrated in 18% and 3% of patients, respectively, who continued taking anakinra (all dose groups) and in 20% and 1% of patients, respectively, who were originally receiving placebo and then were randomized to all doses of anakinra. Anakinra was well tolerated for 76 weeks. The only side effects that appeared to be treatment-related were skin reactions at the injection site. There was no evidence of decreased tolerance, an increased number of withdrawals, or an increased incidence of clinical complications associated with extended anakinra therapy.
The clinical benefits of treatment with daily self-administered subcutaneous injections of anakinra in a cohort of patients with active RA were maintained for up to 48 weeks. Anakinra was well tolerated over 76 weeks. These observations support the long-term use of anakinra for the treatment of patients with RA.
证明人重组白细胞介素-1受体拮抗剂阿那白滞素在类风湿关节炎（RA）患者中的长期疗效，并评估不同日剂量阿那白滞素的长期安全性。
阿那白滞素的疗效和安全性先前已在472例活动性RA患者中进行的一项双盲、安慰剂对照、为期24周的评估中得到证实。在完成该研究安慰剂对照阶段的345例患者中，309例继续参与该研究为期52周的多中心、双盲、平行组扩展阶段。患者每日接受一次皮下注射阿那白滞素（30、75或150mg）。在扩展阶段的前24周（总计48周治疗）对309例患者的疗效进行评估，采用美国风湿病学会综合评分（ACR20）、其各组成部分以及手部和腕部的X线片。在整个52周扩展阶段（总计76周暴露）对所有472例患者的安全性进行评估。
共有218例患者完成扩展阶段。在91例提前退出的患者中，46例因不良事件退出，26例因缺乏疗效退出。进入扩展阶段的接受阿那白滞素治疗的患者中，改善水平维持了48周。第24周时ACR20反应率为51%，第48周时为46%，且在所有剂量组中该效应均一致。对阿那白滞素反应的持续性在持续ACR20反应评估中得到进一步证实，在第一个和第二个24周期间相似（分别为36%和42%）。在第48周时，继续服用阿那白滞素（所有剂量组）的患者中分别有18%和3%达到ACR50和ACR70反应，而最初接受安慰剂然后随机接受所有剂量阿那白滞素治疗的患者中分别有20%和1%达到该反应。阿那白滞素在76周内耐受性良好。唯一似乎与治疗相关的副作用是注射部位的皮肤反应。没有证据表明耐受性降低、退出人数增加或与阿那白滞素延长治疗相关的临床并发症发生率增加。
在一组活动性RA患者中，每日自行皮下注射阿那白滞素治疗的临床益处维持了长达48周。阿那白滞素在76周内耐受性良好。这些观察结果支持阿那白滞素长期用于治疗RA患者。
