Adverse events associated with mesalazine in the real-world: A comprehensive pharmacovigilance analysis of the FAERS and JADER databases.

Objective: We conducted a pharmacovigilance analysis of mesalazine-related adverse events (AEs) in the realworld using the America's FAERS and Japan's JADER databases. Methods: We extracted reports of mesalazine-associated AEs from FAERS and JADER spanning the first quarter of 2004 to the third quarter of 2024. In the disproportionality analysis, we applied the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma-Poisson shrinker (MGPS) algorithms for signal detection. The time to onset of AEs was assessed using Kaplan-Meier curves and the Weibull distribution test. Results: The analysis encompassed 40,265 AEs reports from FAERS and 4,330 from JADER. Mesalazine-related preferred terms (PTs) mapped to 27 System Organ Classes (SOCs) in FAERS and 25 SOCs in JADER. Gastrointestinal disorders emerged as the most frequently reported SOC in both databases. Three SOCs demonstrated significant signal strength across both datasets: (1) gastrointestinal disorders, (2) general disorders and administration site conditions, and (3) respiratory, thoracic, and mediastinal disorders. Common AEs including diarrhœa, pancreatitis, gastroenteritis, asmyopericarditis, proctitis ulcerative, and glutamate dehydrogenase level abnormal aligned with established drug labeling. Notably, novel pharmacovigilance signals were detected for organizing pneumonia (FAERS: n = 113, ROR = 35.21, 95%CI 29.21-42.46; JADER: n = 32, ROR = 7.90, 5.56-11.22) and eosinophilic pneumonia (FAERS: n = 77, ROR = 41.25, 32.87-51.76; JADER: n = 179, ROR = 57.69, 49.26-67.56), both requiring urgent clinical attention. AEs mainly occurred within 30 days (58.36%) with a median onset of 17 days, and the median onset time of female patients (12 days) was shorter than male patients (25 days). Conclusion: This pharmacovigilance study provides clinically significant evidence regarding safety-associated adverse events (AEs) of mesalazine in real-world settings. The detection of novel safety signals, particularly organizing pneumonia and eosinophilic pneumonia, highlights the necessity for enhanced post-marketing surveillance through longitudinal AE monitoring. Our findings contribute to the evolving safety profile of mesalazine and warrant further clinical investigations to validate their clinical relevance and establish causal relationships.