Small molecules for inflammatory bowel disease and the risk of infection and malignancy: A systematic review and meta-Analysis

This meta-analysis aimed to ascertain whether small molecule drugs increase the risk of infection or malignancy in adult IBD patients. A comprehensive search of eight databases was conducted from their inception to November 2023. The risk of infections or malignancies in adult IBD patients treated with JAK inhibitors and S1P receptor modulators was compared. Fixed-effects or random-effects models were performed, and relative risk (RR) and 95 % confidence interval (CI) were calculated. 27 RCTs from 14 studies were included ( n = 10,623). The evidence indicates that small molecule drugs increase the risk of any infections (RR: 1.23, 95 %CI: 1.05–1.44) and herpes zoster (RR: 2.23, 95 %CI: 1.39–3.57). Specifically, UC patients on Filgotinib and Tofacitinib, and CD patients on Upadacitinib, showed elevated risks of any infections (RR: 1.27, 95 % CI: 1.04–1.56; RR: 1.42, 95 % CI: 1.16–1.75; RR: 1.57, 95 % CI: 1.11–2.22). CD patients on Upadacitinib also had a significantly higher risk of herpes zoster (RR: 2.64, 95 %CI: 1.16–5.99). No infections were associated with S1P receptor modulators, and similarly, no malignancies were linked to small molecule drugs. JAK inhibitors increase the risk of any infections and herpes zoster Over a one-year follow-up period in IBD patients. Continuous monitoring of their long-term safety is necessary.