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Risk of tuberculosis in patients treated with TNF-α antagonists: a systematic review and meta-analysis of randomised controlled trials
  1. Zheng Zhang1,
  2. Wei Fan1,2,
  3. Gui Yang3,
  4. Zhigao Xu2,
  5. June Wang1,
  6. Qingyuan Cheng1,
  7. Mingxia Yu1,3
  1. 1Department of Clinical Laboratory & Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
  2. 2Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
  3. 3Department of Clinical Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
  1. Correspondence to Dr Mingxia Yu; dewrosy520{at}


Objectives 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.

Methods 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.

Results 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.

Conclusions 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.

  • TNF-α antagonists
  • meta-analysis
  • RCTs

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  • Contributors All authors conceived of and designed the study. ZZ and WF performed the literature search, data collection and statistical analysis. GY and ZX assessed the quality of articles. ZZ, JW and QC wrote the paper. MY and WF revised the manuscript.

  • Funding This study was supported by the National Natural Science Foundation of China (nos. 81472033 and 30901308), the National Science Foundation of Hubei Province (nos. 2013CFB233 and 2013CFB235), the Scientific and Technological Project of Wuhan City (2014060101010045), Hubei Province Health and Family Planning Scientific Research Project (WJ2015Q021) and Seeding Program of the Science and Technology Innovation from Zhongnan Hospital of Wuhan University (ZNPY2016054).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional data are available.

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