title: The Risk of Tuberculosis in Patients with Rheumatoid Arthritis Treated with Tumor Necrosis Factor-α Antagonist: A Metaanalysis of Both Randomized Controlled Trials and Registry/Cohort Studies.
abstract: OBJECTIVE
  Tumor necrosis factor-α (TNF-α) antagonists have significantly improved treatment results in rheumatoid arthritis (RA), but have also increased the risk of tuberculosis (TB). Etanercept (ETN), adalimumab (ADA), infliximab (IFX), golimumab, and certolizumab pegol are the 5 drugs currently available on the market. This article aimed to evaluate the risk of TB infection from these 5 drugs for patients with RA.
  
  
  METHODS
  We searched PubMed, EMBASE, COCHRANE library, OVID, and EBSCO for randomized controlled trials (RCT) of TNF-α antagonist versus control and registry/longitudinal cohort studies of 1 TNF-α antagonist versus another. The Mantel-Haenszel test was adopted to analyze risk ratio (RR) in this metaanalysis.
  
  
  RESULTS
  Fifty RCT and 13 non-RCT were included in this study. No significant difference in TB risk was found in the RCT because of the short observational periods. In the non-RCT, TNF-α antagonist was associated with a higher TB risk in patients with RA (RR 4.03, 95% CI 2.36-6.88), and the TB incidence rates of IFX and ADA were 2.78 and 3.88 times, respectively, higher than that of ETN. Further, preventive treatment for latent TB infection (LTBI) was shown to reduce the TB risk by 65% (RR 0.35, 95% CI 0.15-0.82).
  
  
  CONCLUSIONS
  This study demonstrated a significant increase in TB risk in patients with RA treated with TNF-α antagonists; among them, ETN is least likely to cause active TB. The study also proposes the necessity of LTBI prophylaxis in patients with RA.
authors.affiliation: From the Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.J.W. Ai, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; S. Zhang, MD, PhD, Department of Infectious Diseases, Huashan Hospital, Fudan University; Q.L. Ruan, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; Y.Q. Yu, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; B.Y. Zhang, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; Q.H. Liu, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; W.H. Zhang, MD, PhD, Department of Infectious Diseases, Huashan Hospital, Fudan University.
authors.forename: Jing-Wen
authors.initials: JW
authors.lastname: Ai
authors.affiliation: From the Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.J.W. Ai, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; S. Zhang, MD, PhD, Department of Infectious Diseases, Huashan Hospital, Fudan University; Q.L. Ruan, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; Y.Q. Yu, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; B.Y. Zhang, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; Q.H. Liu, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; W.H. Zhang, MD, PhD, Department of Infectious Diseases, Huashan Hospital, Fudan University.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: From the Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.J.W. Ai, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; S. Zhang, MD, PhD, Department of Infectious Diseases, Huashan Hospital, Fudan University; Q.L. Ruan, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; Y.Q. Yu, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; B.Y. Zhang, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; Q.H. Liu, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; W.H. Zhang, MD, PhD, Department of Infectious Diseases, Huashan Hospital, Fudan University.
authors.forename: Qiao-Ling
authors.initials: QL
authors.lastname: Ruan
authors.affiliation: From the Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.J.W. Ai, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; S. Zhang, MD, PhD, Department of Infectious Diseases, Huashan Hospital, Fudan University; Q.L. Ruan, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; Y.Q. Yu, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; B.Y. Zhang, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; Q.H. Liu, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; W.H. Zhang, MD, PhD, Department of Infectious Diseases, Huashan Hospital, Fudan University.
authors.forename: Yi-Qi
authors.initials: YQ
authors.lastname: Yu
authors.affiliation: From the Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.J.W. Ai, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; S. Zhang, MD, PhD, Department of Infectious Diseases, Huashan Hospital, Fudan University; Q.L. Ruan, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; Y.Q. Yu, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; B.Y. Zhang, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; Q.H. Liu, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; W.H. Zhang, MD, PhD, Department of Infectious Diseases, Huashan Hospital, Fudan University.
authors.forename: Bing-Yan
authors.initials: BY
authors.lastname: Zhang
authors.affiliation: From the Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.J.W. Ai, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; S. Zhang, MD, PhD, Department of Infectious Diseases, Huashan Hospital, Fudan University; Q.L. Ruan, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; Y.Q. Yu, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; B.Y. Zhang, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; Q.H. Liu, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; W.H. Zhang, MD, PhD, Department of Infectious Diseases, Huashan Hospital, Fudan University.
authors.forename: Qi-Hui
authors.initials: QH
authors.lastname: Liu
authors.affiliation: From the Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.J.W. Ai, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; S. Zhang, MD, PhD, Department of Infectious Diseases, Huashan Hospital, Fudan University; Q.L. Ruan, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; Y.Q. Yu, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; B.Y. Zhang, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; Q.H. Liu, MD, Department of Infectious Diseases, Huashan Hospital, Fudan University; W.H. Zhang, MD, PhD, Department of Infectious Diseases, Huashan Hospital, Fudan University. zhangwenhong@fudan.edu.cn.
authors.forename: Wen-Hong
authors.initials: WH
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology* / Q000503:physiopathology; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016867:Immunocompromised Host; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012016:Reference Values; D012042:Registries; D012720:Severity of Illness Index; D014376:Tuberculosis / Q000139:chemically induced* / Q000453:epidemiology* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000037:antagonists & inhibitors*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014409:Tumor Necrosis Factor-alpha
keywords: RHEUMATOID ARTHRITIS; TUBERCULOSIS; TUMOR NECROSIS FACTOR-α ANTAGONISTS