Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2018; 24(25): 2764-2775
Published online Jul 7, 2018. doi: 10.3748/wjg.v24.i25.2764
Systematic review and meta-analysis on the association of tuberculosis in Crohn’s disease patients treated with tumor necrosis factor-α inhibitors (Anti-TNFα)
Brent L Cao, Ahmad Qasem, Robert C Sharp, Latifa S Abdelli, Saleh A Naser
Brent L Cao, Ahmad Qasem, Robert C Sharp, Latifa S Abdelli, Saleh A Naser, Division of Molecular Microbiology, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, United States
Author contributions: Cao BL and Qasem A are Co-first authors; Cao BL designed the study, acquired the data, analyzed and interpreted the data, and participating in writing the manuscript; Qasem A, Sharp RC, and Abdelli LS interpreted the data and participated in revisions of the manuscript; Naser SA is the group leader who supervised all aspects of the data collection/analyses and manuscript writing.
Conflict-of-interest statement: The authors declare that they have no competing interests.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Saleh A Naser, PhD, Professor, Associate Director, Burnett School of Biomedical Sciences, Division of Molecular Microbiology, College of Medicine, University of Central Florida, 4110 Libra Drive, Orlando, FL 32816, United States.
Telephone: +1-407-8230955 Fax: +1-407-8230955
Received: April 12, 2018
Peer-review started: April 13, 2018
First decision: April 27, 2018
Revised: April 30, 2018
Accepted: June 2, 2018
Article in press: June 2, 2018
Published online: July 7, 2018

To perform a meta-analysis on the risk of developing Mycobacterium tuberculosis (TB) infection in Crohn’s disease (CD) patients treated with tumor necrosis factor-alpha (TNFα) inhibitors.


A meta-analysis of randomized, double-blind, placebo-controlled trials of TNFα inhibitors for treatment of CD in adults was conducted. Arcsine transformation of TB incidence was performed to estimate risk difference. A novel epidemiologically-based correction (EBC) enabling inclusions of studies reporting no TB infection cases in placebo and treatment groups was developed to estimate relative odds.


Twenty-three clinical trial studies were identified, including 5669 patients. Six TB infection cases were reported across 5 studies, all from patients receiving TNFα inhibitors. Eighteen studies reported no TB infection cases in placebo and TNFα inhibitor treatment arms. TB infection risk was significantly increased among patients receiving TNFα inhibitors, with a risk difference of 0.028 (95%CI: 0.0011-0.055). The odds ratio was 4.85 (95%CI: 1.02-22.99) with EBC and 5.85 (95%CI: 1.13-30.38) without EBC.


The risk of TB infection is higher among CD patients receiving TNFα inhibitors. Understanding the immunopathogenesis of CD is crucial, since using TNFα inhibitors in these patients could favor mycobacterial infections, particularly Mycobacterium avium subspecies paratuberculosis, which ultimately could worsen their clinical condition.

Keywords: Tuberculosis, Tumor necrosis factor-alpha inhibitors, Crohn’s Disease, Meta-analysis, Systematic review

Core tip: The increased risk of Mycobacterium tuberculosis (TB) and other Mycobacterium species when on tumor necrosis factor-alpha (TNFα) inhibitor treatments has been a problem in patients with autoimmune disorders, such as Crohn’s disease (CD). This meta-analysis examines in detail the clinical trials that involve CD patients on TNFα inhibitors and their risk of developing TB infections. Our data concludes that, out of twenty-three studies examined, TNFα inhibitors are indeed associated with an increased risk of TB infection in CD patients. Knowledge of this data could help re-analyze what medications autoimmune patients should be prescribed to and evaluate possible linkages to Mycobacterium avium subspecies paratuberculosis infection. Thus, this information should be used to further inform clinical decision making and research.