Drug-associated inflammatory bowel disease: a real-world pharmacovigilance study using the FAERS and JADER databases.

Background: Although several medications have been linked to inflammatory bowel disease (IBD), the association between most drugs and IBD remains unclear. This study aimed to identify medications most frequently reported in connection with IBD by analyzing large-scale data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japan Adverse Drug Event Report (JADER) database. Methods: We extracted reports of drug-associated IBD adverse events from FAERS and performed external validation using JADER. Disproportionality analyses of suspected drugs were conducted using four methods: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS). Additional analyses included time-to-onset (TTO) assessment, Weibull distribution modeling, and subgroup analyses by age, sex, and IBD subtype to evaluate signal stability and clinical characteristics. Results: The FAERS database yielded 52,395 reports of drug-associated IBD, corresponding to 50,426 patients.Females accounted for a higher proportion of reports than males, with the majority of cases occurring in individuals aged 18-64 years. The annual number of reports showed an overall upward trend. Among drugs reported at least 50 times, 17 met all four algorithmic threshold criteria and were classified as positive signals. Anti-tumor necrosis factor-alpha (anti-TNF-α) inhibitors ranked highest by reporting frequency, whereas isotretinoin demonstrated the strongest signal intensity. External validation using JADER confirmed consistent signals for certain anti-TNF-α inhibitors, anti-interleukin biologic agents, conventional immunosuppressants, and antibiotics. Time-to-onset analysis revealed that the median onset of IBD occurred within one year for most drug-associated cases. The Weibull model indicated an "early failure-type" onset pattern for the majority of positive signals. Conclusion: From a pharmacovigilance perspective, this study provides a comprehensive overview of medications associated with IBD, offering clinically relevant insights. Our findings deliver real-world evidence to support the identification and monitoring of drug-associated IBD; however, confirmation in large prospective cohort studies remains necessary.