Comparative effectiveness and safety of biological treatment options after tumour necrosis factor α inhibitor failure in rheumatoid arthritis: systematic review and indirect pairwise meta-analysis
Comparative effectiveness and safety of biological treatment options after tumour necrosis factor α inhibitor failure in rheumatoid arthritis: systematic review and indirect pairwise meta-analysis
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DOI：
10.1136/annrheumdis-2011-200490
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发表时间：
2012-08-01
影响因子：
27.4
通讯作者：
Wong, John B.
中科院分区：
文献类型：
--
作者：
Schoels, Monika;Aletaha, Daniel;Wong, John B.
目的比较肿瘤坏死因子-α抑制剂治疗类风湿性关节炎后生物制剂的疗效和安全性。方法利用Medline和Cochrane数据库进行系统的文献检索，检索http://www.clinicaltrials.gov，，手工检索文献。纳入纳入有TNFi-IR的RA患者的随机、安慰剂对照试验，以美国风湿病学会(ACR)的反应为主要疗效结果，提取不良事件(AEs)、严重不良事件(SAEs)和严重感染(SIS)作为安全措施。结果在4个随机对照试验中，abatacept、Golimumab、rituximab和tocilizumab与安慰剂的直接比较显示，ACR20、ACR50和ACR70的平均OR值分别为3.3-8.9、5.5-10.2和4.1-13.5，具有统计学意义。与安慰剂相比，AEs、SAEs和SIS的风险并不显著。四种生物制剂的间接配对比较显示，ACR50和ACR70没有显著差异。Golimumab对ACR20的OR显著降低(0.56~0.59)，但AEs显著减少(RD 0.13~0.18)。不同生物制剂对一次或多次TNFi失败后的疗效无显著差异。结论在对一种或多种TNFi无效的患者中，新的生物制剂提供了显著的改善和良好的安全性。由于缺乏面对面的试验，间接荟萃分析能够比较生物制剂之间的有效性和安全性，并表明所有生物制剂都有类似的效果。
Background Optimal treatment for rheumatoid arthritis (RA) after inadequate response (IR) to tumour necrosis factor alpha inhibitors (TNFi) remains uncertain.Objective To compare the efficacy and safety of biological agents after TNFi-IR.Methods A systematic literature search was carried out using Medline and Cochrane databases, as well as http://www.clinicaltrials.gov, and bibliographies of the retrieved literature were searched by hand. Randomised, placebo-controlled trials that enrolled patients with RA with TNFi-IR were included and American College of Rheumatology (ACR) response as primary efficacy outcome and adverse events (AEs), serious adverse events (SAEs) and serious infections (SIs) as safety measures were extracted. An indirect meta-analysis with pairwise comparisons of efficacy and safety data was then carried out using ORs or risk differences (RDs) in a random effects model.Results In four randomised controlled trials with 24 weeks' follow-up, direct comparisons of abatacept, golimumab, rituximab and tocilizumab versus placebo showed statistically significant mean ORs of 3.3-8.9 for ACR20, 5.5-10.2 for ACR50 and 4.1-13.5 for ACR70. Risks of AEs, SAEs and SIs versus placebo were non-significant. Indirect pairwise comparisons of the four biological agents showed no significant differences in ACR50 and ACR70. Golimumab had a significantly lower OR (0.56-0.59) for ACR20 but significantly fewer AEs (RD 0.13-0.18). Efficacy after one versus multiple TNFi failures did not differ significantly between the different biological agents.Conclusion In patients refractory to one or more TNFi, new biological agents provide significant improvement with good safety. Lacking head-to-head trials, indirect meta-analysis enables a comparison of effectiveness and safety of biological agents with each other and shows that all biological agents have similar effects.