Systematic review and meta-analysis on the association of tuberculosis in Crohn’s disease patients treated with tumor necrosis factor-α inhibitors (Anti-TNFα)

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.