Abstract
BACKGROUND: Ustekinumab (UST), a monoclonal antibody that blocks the p40 subunit of both interleukin (IL)-12 and IL-23, is widely used in inflammatory bowel disease (IBD) treatment. As UST use continues to increase in real-world clinical practice, it is becoming increasingly imperative to establish a more comprehensive understanding of its safety profile. The aim was to assess the safety of UST treatment in patients with IBD. METHODS: Data on adverse events experienced by UST-treated patients with IBD were extracted from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) for the period of Q4 2009-Q4 2024. Disproportionality was assessed using four statistical measures, including the reporting odds ratio, proportional reporting ratio, multi‑item gamma‑Poisson shrinker method, and Bayesian confidence propagation neural network model. Furthermore, a Weibull distribution analysis was conducted to model the time‑to‑onset of adverse events. RESULTS: A total of 22687 reports identified UST as the primary suspect drug for IBD and covered 27 system organ classes (SOCs), with injury, poisoning and procedural complications (n = 13676), gastrointestinal disorders (n = 9563), and infections and infestations (n = 8035) being the three with the highest frequency. Positive signals led to the identification of potential adverse events that are not widely documented in the labeling, including urinary tract infections, seizures, hepatic enzyme upregulation, hepatic steatosis, cholelithiasis, cerebrovascular accidents, and transient ischemic attacks. Furthermore, UST‑related adverse events follow an early‑failure model, and their reports gradually decline as treatment duration lengthens. CONCLUSIONS: This study provides comprehensive real-world insights into the safety of UST use in IBD treatment, corroborating known adverse reactions and identifying additional potential risks. Robust pharmacovigilance and long-term monitoring are essential to support personalized UST therapy and facilitate informed risk-benefit assessments.