Pharmacovigilance analysis of infliximab in inflammatory bowel disease: novel safety signals and sex-specific adverse event profiles from the FAERS database (2004-2024).

Introduction: Inflammatory bowel disease (IBD) is a chronic immune-mediated gastrointestinal disease, and its global incidence is on the rise, which seriously affects the quality of life of patients. Infliximab is the key therapeutic drug for IBD, and a comprehensive safety assessment is needed. In this pharmacovigilance study, we investigated the adverse events (AE) of infliximab in IBD patients by analyzing the reports submitted to the FDA's Adverse Event Reporting System (FAERS) database. Methods: We analyzed the reports of AEs related to infliximab in FAERS database (2004-2024). Disproportionality analysis (ROR, PRR, BCPNN) was used to identify the safety signals in the general population and gender subgroups. Based on the model of ROR, the influence of gender difference and combined medication was evaluated. The onset time (TTO) and Weibull shape parameter (WSP) were used to analyze and evaluate the occurrence time and risk trend of AEs. Results: Among 80,138 AE reports, 57 Preferred Term (PT) and 14 System Organ Classification (SOC) signals were detected (ROR025 > 1, PRR > 2, χ² > 4, N ≥ 3, IC025 > 0). Some emerging AE signals, such as Horner's syndrome and Henoch-Schoenlein Henoch-Schonlein purpura nephritis (not mentioned in the drug label), suggest that there are new safety hazards. Females (50.7%) exhibited 67 signals, predominantly immune-related (e.g., lupus-like syndrome, N = 1028, ROR = 7.09), while males (41.8%) showed 42 signals, mainly cardiovascular (e.g., blood pressure fluctuation, ROR = 29.33) and infectious. Combined medication (67.3%) will increase cardiovascular risk, while monotherapy is associated with immune/tumor-related AEs (such as breast cancer, ROR = 1.2). Kidney and urinary system diseases (ROR = 21.84) are an under-reported problem. Time trade-off analysis (TTO, N = 15,682) showed that the median treatment duration was 620 days, and the early treatment failed (Weibull β=0.73). In addition, there was a significant gender difference in the incidence of AEs related to infliximab in IBD patients. Conclusion: This study emphasizes that there is a significant burden of AEs in IBD patients treated with infliximab, and finds new safety signals that need further verification. The characteristics of gender-specific AEs suggest that gender-specific monitoring is needed. Women have a higher risk of immune/tumor events, while men have a higher risk of cardiovascular/infectious AEs. Combined medication will aggravate cardiovascular risk, while monotherapy will increase immune/carcinogenic risk. The occurrence of early AEs highlights the necessity of early close monitoring. These findings suggest that pharmacovigilance needs to be improved to optimize the safety of infliximab.