The Comparative Safety of Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis: A Meta-analysis Update of 44 Trials
The Comparative Safety of Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis: A Meta-analysis Update of 44 Trials
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DOI：
10.1016/j.amjmed.2014.06.012
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发表时间：
2014-12-01
影响因子：
5.9
通讯作者：
Choi, Hyon K.
中科院分区：
文献类型：
--
作者：
Michaud, Tzeyu L.;Rho, Young Hee;Choi, Hyon K.
目的：本研究的目的是评估和更新肿瘤坏死因子抑制剂治疗类风湿关节炎患者的随机对照试验的安全性数据。方法：从1990年至2013年5月进行了系统的文献检索。纳入的所有研究均为类风湿性关节炎患者的随机、双盲、对照试验，评价阿达木单抗、聚乙二醇赛妥珠单抗、依那西普、戈利木单抗或英夫利昔单抗治疗。结果：纳入44项随机对照试验，包括11,700例接受肿瘤坏死因子抑制剂治疗的受试者和5901例接受安慰剂或传统疾病缓解抗风湿药物治疗的受试者。与安慰剂和传统的缓解疾病的抗风湿药物治疗相比，肿瘤坏死因子抑制剂治疗作为一个组与更高的严重感染风险（OR，1.42; 95%置信区间[CI]，1.13-1.78）和因不良事件而停药的风险（OR，1.23; 95% CI，1.06-1.43）相关。具体而言，服用阿达木单抗、赛妥珠单抗和英夫利西单抗的患者发生严重感染的风险增加（OR分别为1.69、1.98和1.63），因不良事件而停药的风险增加（OR分别为1.38、1.67和2.04）。相比之下，服用依那西普的患者因不良事件而停药的风险降低（OR，0.72; 95% CI，0.55-0.93）。虽然在不同的肿瘤坏死因子抑制剂的恶性肿瘤的OR变化，没有达到统计学意义。结论：这些荟萃分析更新的肿瘤坏死因子抑制剂的比较安全性表明，阿达木单抗，赛妥珠单抗，英夫利昔单抗，这似乎有助于更高的停药率相关的严重感染的风险更高。相比之下，使用依那西普的停药率较低。这些数据可能有助于指导临床比较类风湿关节炎的管理决策。(C)2014爱思唯尔公司All rights reserved.
OBJECTIVE: The study objective was to evaluate and update the safety data from randomized controlled trials of tumor necrosis factor inhibitors in patients treated for rheumatoid arthritis.METHODS: A systematic literature search was conducted from 1990 to May 2013. All studies included were randomized, double-blind, controlled trials of patients with rheumatoid arthritis that evaluated adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab treatment. The serious adverse events and discontinuation rates were abstracted, and risk estimates were calculated by Peto odds ratios (ORs).RESULTS: Forty-four randomized controlled trials involving 11,700 subjects receiving tumor necrosis factor inhibitors and 5901 subjects receiving placebo or traditional disease-modifying antirheumatic drugs were included. Tumor necrosis factor inhibitor treatment as a group was associated with a higher risk of serious infection (OR, 1.42; 95% confidence interval [CI], 1.13-1.78) and treatment discontinuation due to adverse events (OR, 1.23; 95% CI, 1.06-1.43) compared with placebo and traditional disease-modifying antirheumatic drug treatments. Specifically, patients taking adalimumab, certolizumab pegol, and infliximab had an increased risk of serious infection (OR, 1.69, 1.98, and 1.63, respectively) and showed an increased risk of discontinuation due to adverse events (OR, 1.38, 1.67, and 2.04, respectively). In contrast, patients taking etanercept had a decreased risk of discontinuation due to adverse events (OR, 0.72; 95% CI, 0.55-0.93). Although ORs for malignancy varied across the different tumor necrosis factor inhibitors, none reached statistical significance.CONCLUSIONS: These meta-analysis updates of the comparative safety of tumor necrosis factor inhibitors suggest a higher risk of serious infection associated with adalimumab, certolizumab pegol, and infliximab, which seems to contribute to higher rates of discontinuation. In contrast, etanercept use showed a lower rate of discontinuation. These data may help guide clinical comparative decision making in the management of rheumatoid arthritis. (C) 2014 Elsevier Inc. All rights reserved.