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生物制剂治疗类风湿关节炎的比较疗效:系统评价与网状Meta分析

Comparative effectiveness of biologics for the management of rheumatoid arthritis: systematic review and network meta-analysis.

作者信息

Alfonso-Cristancho Rafael, Armstrong Nigel, Arjunji Ramesh, Riemsma Rob, Worthy Gill, Ganguly Rita, Kleijnen Jos

机构信息

GlaxoSmithKline, Collegeville, PA, USA.

Kleijnen Systematic Reviews Ltd, York, UK.

出版信息

Clin Rheumatol. 2017 Jan;36(1):25-34. doi: 10.1007/s10067-016-3435-2. Epub 2016 Oct 10.

Abstract

Our aim was to establish the comparative effectiveness of rheumatoid arthritis (RA) biologics, using a systematic review and network meta-analysis. The systematic review used randomized controlled trials (RCTs) in adults with RA who failed treatment with conventional disease-modifying agents for rheumatoid disease (cDMARDs). We compared the effectiveness of abatacept, adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, and rituximab to tocilizumab, a recent biologic with a different mechanism of action (anti-IL-6 receptor). A network meta-analysis (NMA) included the indirect and direct evidence previously selected. In total, 207 articles were included describing 68 RCTs. The NMA showed that tocilizumab monotherapy was superior to standard care (ACR20, OR 13.27, 95 % CrI [3.958, 43.98]; ACR50, 17.45 [10.18, 31.24]; ACR70, 37.77 [7.226, 216.3]; EULAR, 10.42 [1.963, 54.8]); and methotrexate (MTX; ACR50, OR 5.44 [4.142, 7.238]; ACR70, 7.364 [1.4, 30.83]; EULAR, 4.226 [1.184, 15.58]) at 26 weeks. Similarly, the combination of tocilizumab + MTX was significantly better than standard care/placebo and MTX alone for ACR20, ACR50, ACR70, and EULAR at 26 weeks (OR 18.63 [5.32, 66.81]; 24.27 [14.5, 41.91]; 46.13 [10.08, 277]; 14.23 [2.493, 84.02]; 4.169 [2.267, 7.871]; 5.44 [4.142, 7.238]; 8.731 [4.203, 19.29]; 7.306 [4.393, 13.04], respectively). At 52 weeks, compared to MTX alone, tocilizumab + MTX was significantly better for ACR20 and ACR50 response. Few significant differences were found between tocilizumab (alone or in combination) and any other biologics. Results must be considered in context with the limitations of the available evidence. This NMA suggests that tocilizumab was superior to cDMARDs and as effective as other biologics for RA.

摘要

我们的目标是通过系统评价和网状Meta分析,确定类风湿关节炎(RA)生物制剂的相对疗效。该系统评价纳入了使用传统抗风湿疾病改善病情药物(cDMARDs)治疗失败的成年RA患者的随机对照试验(RCT)。我们比较了阿巴西普、阿达木单抗、依那西普、英夫利昔单抗、赛妥珠单抗、戈利木单抗和利妥昔单抗与托珠单抗(一种作用机制不同的新型生物制剂,抗IL-6受体)的疗效。网状Meta分析(NMA)纳入了之前筛选出的间接和直接证据。总共纳入了207篇文章,描述了68项RCT。NMA显示,在26周时,托珠单抗单药治疗优于标准治疗(美国风湿病学会20%改善率[ACR20],比值比[OR]13.27,95%可信区间[CrI][3.958, 43.98];ACR50,17.45[10.18, 31.24];ACR70,37.77[7.226, 216.3];欧洲抗风湿病联盟[EULAR]反应,10.42[1.963, 54.8])以及甲氨蝶呤(MTX;ACR50,OR 5.44[4.142, 7.238];ACR70,7.364[1.4, 30.83];EULAR反应,4.226[1.184, 15.58])。同样,在26周时,托珠单抗+MTX联合治疗在ACR20、ACR50、ACR70和EULAR反应方面显著优于标准治疗/安慰剂和单用MTX(OR分别为18.63[5.32, 66.81];24.27[14.5, 41.91];46.13[10.08, 277];14.23[2.493, 84.02];4.169[2.267, 7.871];5.44[4.142, 7.238];8.731[4.203, 19.29];7.306[4.393, 13.04])。在52周时,与单用MTX相比,托珠单抗+MTX在ACR20和ACR50反应方面显著更好。在托珠单抗(单用或联合使用)与任何其他生物制剂之间未发现显著差异。必须结合现有证据的局限性来考虑这些结果。该NMA表明,托珠单抗优于cDMARDs,并且在治疗RA方面与其他生物制剂疗效相当。

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