Risk of tuberculosis in patients treated with TNF-α antagonists: a systematic review and meta-analysis of randomised controlled trials.
Risk of tuberculosis in patients treated with TNF-α antagonists: a systematic review and meta-analysis of randomised controlled trials.
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TNF-α拮抗剂治疗患者的结核病风险：随机对照试验的系统评价和荟萃分析
DOI：
10.1136/bmjopen-2016-012567
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发表时间：
2017-03-22
期刊：
影响因子：
2.9
通讯作者：
Yu M
中科院分区：
文献类型：
--
作者：
Zhang Z;Fan W;Yang G;Xu Z;Wang J;Cheng Q;Yu M
据报道，接受TNF-α拮抗剂治疗的患者患结核病（TB）的风险增加，这是WHO黑盒警告中强调的一个问题。本综述旨在评估接受TNF-α拮抗剂治疗的患者发生TB的风险。在MEDLINE、Embase和科克伦图书馆中对随机对照试验（RCT）进行系统性文献检索，并根据预定标准选择纳入研究。使用随机效应模型计算OR和95% CI。亚组分析考虑了药物类型、疾病和结核病流行的影响。使用推荐、评估、发展和评价等级（GRADE）方法评估证据质量。纳入了涉及11879例患者的29项RCT（英夫利西单抗14项，阿达木单抗9项，戈利木单抗2项，依那西普1项，赛妥珠单抗3项）。在分配至TNF-α拮抗剂组的7912例患者中，45例（0.57%）发生TB，而分配至对照组的3967例患者中仅发生3例，OR为1.94（95% CI 1.10 - 3.44，p=0.02）。亚组分析表明，类风湿性关节炎（RA）患者接受TNF-α拮抗剂治疗时，TB风险增加更高（OR 2.29（1.09至4.78），p=0.03）。GRADE系统推荐的证据等级为“低”。我们的荟萃分析结果表明，接受TNF-α拮抗剂治疗的患者患TB的风险可能显著增加。然而，TNF-α拮抗剂治疗导致TB风险增加的生物学机制仍需进一步研究。
An increased risk of tuberculosis (TB) has been reported in patients treated with TNF-α antagonists, an issue that has been highlighted in a WHO black box warning. This review aimed to assess the risk of TB in patients undergoing TNF-α antagonists treatment. A systematic literature search for randomised controlled trials (RCTs) was performed in MEDLINE, Embase and Cochrane library and studies selected for inclusion according to predefined criteria. ORs with 95% CIs were calculated using the random-effect model. Subgroup analyses considered the effects of drug type, disease and TB endemicity. The quality of evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. 29 RCTs involving 11 879 patients were included (14 for infliximab, 9 for adalimumab, 2 for golimumab, 1 for etanercept and 3 for certolizumab pegol). Of 7912 patients allocated to TNF-α antagonists, 45 (0.57%) developed TB, while only 3 cases occurred in 3967 patients allocated to control groups, resulting in an OR of 1.94 (95% CI 1.10 to 3.44, p=0.02). Subgroup analyses indicated that patients of rheumatoid arthritis (RA) had a higher increased risk of TB when treated with TNF-α antagonists (OR 2.29 (1.09 to 4.78), p=0.03). The level of the evidence was recommended as ‘low’ by the GRADE system. Findings from our meta-analysis indicate that the risk of TB may be significantly increased in patients treated with TNF-α antagonists. However, further studies are needed to reveal the biological mechanism of the increased TB risk caused by TNF-α antagonists treatment.