Singh Jasvinder A, Christensen Robin, Wells George A, Suarez-Almazor Maria E, Buchbinder Rachelle, Lopez-Olivo Maria Angeles, Tanjong Ghogomu Elizabeth, Tugwell Peter
Medicine, Minneapolis VA Medical Center, 1 Veterans Drive, Rheumatology (111R), Minneapolis, MN, USA, 55417.
Cochrane Database Syst Rev. 2009 Oct 7;2009(4):CD007848. doi: 10.1002/14651858.CD007848.pub2.
The biologic disease-modifying anti-rheumatic drugs (DMARDs) are very effective in treating rheumatoid arthritis (RA), however there is a lack of head-to-head comparison studies.
To compare the efficacy and safety of abatacept, adalimumab, anakinra, etanercept, infliximab, and rituximab in patients with RA.
This 'Overview of Reviews' was done by including all Cochrane Reviews on Biologics for RA available in The Cochrane Library. We included only data on standard dosing regimens for these biologic DMARDs from placebo-controlled trials. The primary efficacy and safety outcomes were ACR50 and withdrawals due to adverse events. We calculated Risk Ratios (RR) for efficacy, Odds Ratio (OR) for safety and combined estimates of events across the placebo groups as the expected Control Event Rate (CER). Indirect comparisons of biologics were performed for efficacy and safety using a hierarchical linear mixed model incorporating the most important study-level characteristic (i.e. type of biologic) as a fixed factor and study as a random factor; reducing the between study heterogeneity by adjusting for the interaction between the proportion of patients responding on placebo and the duration of the trial.
From the six available Cochrane reviews, we obtained data from seven studies on abatacept, eight on adalimumab, five on anakinra, four on etanercept, four on infliximab, and three on rituximab.The indirect comparison estimates showed similar efficacy for the primary efficacy outcome for all biologics with three exceptions. Anakinra was less efficacious than etanercept with a ratio of RRs (95% CI; P value) of 0.44 (0.23 to 0.85; P = 0.014); anakinra was less efficacious than rituximab, 0.45 (0.22 to 0.90; P = 0.023); and likewise adalimumab was more efficacious than anakinra, 2.34 (1.32 to 4.13; P = 0.003).In terms of safety, adalimumab was more likely to lead to withdrawals compared to etanercept, with a ratio of ORs of 1.89 (1.18 to 3.04; P = 0.009); anakinra more likely than etanercept, 2.05 (1.27 to 3.29; P = 0.003); and likewise etanercept less likely than infliximab, 0.37 (0.19 to 0.70; P = 0.002).
AUTHORS' CONCLUSIONS: Based upon indirect comparisons, anakinra seemed less efficacious than etanercept, adalimumab and rituximab and etanercept seemed to cause fewer withdrawals due to adverse events than adalimumab, anakinra and infliximab. Significant heterogeneity in characteristics of trial populations imply that these finding must be interpreted with caution. These findings can inform physicians and patients regarding their choice of biologic for treatment of RA.
生物性疾病改善抗风湿药物（DMARDs）在治疗类风湿关节炎（RA）方面非常有效，然而缺乏直接对比研究。
比较阿巴西普、阿达木单抗、阿那白滞素、依那西普、英夫利昔单抗和利妥昔单抗在RA患者中的疗效和安全性。
本“综述概述”通过纳入Cochrane图书馆中所有关于生物制剂治疗RA的Cochrane综述完成。我们仅纳入了来自安慰剂对照试验的这些生物性DMARDs标准给药方案的数据。主要疗效和安全性结局为美国风湿病学会（ACR）50反应率及因不良事件导致的停药率。我们计算了疗效的风险比（RR）、安全性的比值比（OR），并将安慰剂组事件的合并估计值作为预期对照事件率（CER）。使用分层线性混合模型对生物制剂的疗效和安全性进行间接比较，该模型将最重要的研究水平特征（即生物制剂类型）作为固定因子，研究作为随机因子；通过调整安慰剂反应患者比例与试验持续时间之间的相互作用来减少研究间的异质性。
从六项可用的Cochrane综述中，我们获得了七项关于阿巴西普研究的数据、八项关于阿达木单抗研究的数据、五项关于阿那白滞素研究的数据、四项关于依那西普研究的数据、四项关于英夫利昔单抗研究的数据以及三项关于利妥昔单抗研究的数据。间接比较估计显示，除三个例外情况外，所有生物制剂在主要疗效结局方面疗效相似。阿那白滞素的疗效低于依那西普，RR比值（95%CI；P值）为0.44（0.23至0.85；P = 0.014）；阿那白滞素的疗效低于利妥昔单抗，为0.45（0.22至0.90；P = 0.023）；同样，阿达木单抗的疗效高于阿那白滞素，为2.34（1.32至4.13；P = 0.003）。在安全性方面，与依那西普相比，阿达木单抗更易导致停药，OR比值为1.89（1.18至3.04；P = 0.009）；阿那白滞素比依那西普更易导致停药，为2.05（1.27至3.29；P = 0.003）；同样，依那西普比英夫利昔单抗导致停药的可能性更小，为0.37（0.19至0.70；P = 0.002）。
基于间接比较，阿那白滞素的疗效似乎低于依那西普、阿达木单抗和利妥昔单抗，且依那西普因不良事件导致停药的情况似乎比阿达木单抗、阿那白滞素和英夫利昔单抗更少。试验人群特征存在显著异质性，这意味着这些发现必须谨慎解读。这些发现可为医生和患者在选择治疗RA的生物制剂时提供参考。
