Zhang Zheng, Fan Wei, Yang Gui, Xu Zhigao, Wang June, Cheng Qingyuan, Yu Mingxia
Department of Clinical Laboratory & Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
BMJ Open. 2017 Mar 22;7(3):e012567. doi: 10.1136/bmjopen-2016-012567.
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.
有报道称，接受肿瘤坏死因子-α（TNF-α）拮抗剂治疗的患者患结核病（TB）的风险增加，这一问题已在世卫组织的黑框警告中得到强调。本综述旨在评估接受TNF-α拮抗剂治疗的患者患结核病的风险。
在MEDLINE、Embase和Cochrane图书馆中对随机对照试验（RCT）进行系统的文献检索，并根据预定义标准选择纳入研究。使用随机效应模型计算95%置信区间的比值比（OR）。亚组分析考虑了药物类型、疾病和结核病流行情况的影响。使用推荐分级、评估、制定和评价（GRADE）方法评估证据质量。
纳入了29项涉及11879例患者的随机对照试验（英夫利昔单抗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7912例分配接受TNF-α拮抗剂治疗的患者中，45例（0.57%）发生结核病，而在3967例分配到对照组的患者中仅发生3例，OR为1.94（95%CI 1.10至3.44，p=0.02）。亚组分析表明，类风湿关节炎（RA）患者接受TNF-α拮抗剂治疗后患结核病的风险增加更高（OR 2.29（1.09至4.78），p=0.03）。GRADE系统将证据水平推荐为“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结核病的风险可能会显著增加。然而，需要进一步研究以揭示TNF-α拮抗剂治疗导致结核病风险增加的生物学机制。
