Analysis of Onset Timing and Risk Factors for Mesalazine-related Adverse Events Using the JADER Database

Mesalazine is a cornerstone therapy in the treatment of inflammatory bowel disease (IBD). Although formulated for local action, it can cause serious adverse events (AEs), such as interstitial lung disease and myocarditis, as well as mesalazine-specific drug intolerance. However, the timing of onset and associated risk factors remain insufficiently understood. This study aimed to analyze the onset timing and risk factors for mesalazine-related AEs using the Japanese Adverse Drug Event Report (JADER) database to provide pharmacists with essential information for effective monitoring of AEs.

Reporting odds ratios (RORs) for mesalazine-associated AEs in the JADER database were calculated to detect safety signals. Time-to-onset analyses were performed to classify patterns of mesalazine-induced AEs. Risk factors for mesalazine-induced drug intolerance were further evaluated using multivariate logistic regression analysis.

Among the 25 prespecified AEs, signals were detected for 15. Nine AEs were classified as early onset, and one as late-onset. Male sex and the concomitant use of budesonide, golimumab, vedolizumab, and upadacitinib were significantly detected signals of drug intolerance (all p-values <0.01).

Most mesalazine-associated AEs occurred shortly after treatment initiation, although some manifested later. Although direct risk quantification could not be performed from individual RORs, the indicated factors associated with mesalazine intolerance-including sex and specific concomitant drugs might be useful as items for monitoring AEs. These findings provide meaningful insights that may contribute to optimizing therapeutic strategies and improving the quality of life of patients with IBD.