Tuberculosis risk in patients with Crohn's disease on biologics: a retrospective analysis of the Japanese Medical Claims Database

Background/Aims: Treatment using tumor necrosis factor-alpha alpha (TNF-alpha) alpha ) inhibitors is one of the risk factors for active tuberculosis (TB) in patients with Crohn's disease (CD). Biologics, such as ustekinumab (UST) and vedolizumab (VDZ), are less likely to cause opportunistic infections. However, large-scale studies for active TB and biologics other than TNF-alpha alpha inhibitors are limited. We aimed to investigate the association between biologics and active TB utilizing a Japanese medical claims database. Methods: We analyzed retrospectively the association of the risk of active TB development with treatment using TNF-alpha alpha inhibitors and other biologics (UST and VDZ) in patients with CD using the Japanese Medical Data Vision (MDV) database between April 2008 and June 2022. The durations of each biologic and biologic-free treatment were calculated for each patient. Univariate and multivariate analyses were performed using the Cox proportional hazards model, with the utilization of biologics considered as time-dependent covariates. Results: We included 28,811 patients with CD in MDV database. Finally, 17,169 patients were analyzed. In total, 7,064 patients were categorized as biologic-na & iuml;ve, while 10,105 were classified as biologic-experienced. Seventeen patients developed active TB, including 7 on infliximab, 5 on adalimumab, and 5 on no biologics. None of the patients treated with UST and VDZ developed active TB. Multivariate analysis suggested that TNF-alpha alpha inhibitors were the risk factors for active TB (hazard ratio, 3.66; P = 0.020). Conclusions: TNF-alpha alpha inhibitors, but not UST or VDZ, are risk factors for active TB in Japanese patients with CD. (Intest Res, Published online )