Supplementary Material for: Real-world adherence and relapse risk in mesalamine treatment for ulcerative colitis: insights from a large Japanese medical claims database

Introduction
5-Aminosalicylic acid (5-ASA, mesalamine) is the cornerstone for maintaining remission in mild-to-moderate ulcerative colitis (UC), with several formulations available. Non-adherence to mesalamine is associated with increased relapse risk, however, large-scale real-world data comparing adherence and relapse among different formulations remain limited. This study aimed to evaluate adherence and relapse risk among four 5-ASA formulations using a large Japanese healthcare database.

Methods
Using a Japanese nationwide claims database, we retrospectively analyzed UC patients who were prescribed any of four oral 5-ASA formulations—time-dependent mesalamine, pH-dependent mesalamine, Multi Matrix System (MMX) mesalamine, or salazosulfapyridine—between 2008 and 2022. Adherence was assessed using the proportion of days covered (PDC), and relapse was defined as UC-related hospitalization or escalation of therapy. A Cox proportional hazards model was used to identify factors associated with relapse.

Results
Among 13,876 eligible patients, MMX mesalamine showed the highest adherence (mean PDC: 91.6%) and the lowest relapse rate (2.9%), while salazosulfapyridine had the highest relapse rate (14.8%). In multivariate analysis, pH-dependent mesalamine (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.51–0.72) and MMX mesalamine (HR, 0.53; 95% CI, 0.35–0.78) significantly reduced relapse risk compared to time-dependent mesalamine, whereas salazosulfapyridine (HR, 1.51; 95% CI, 1.32–1.73) significantly increased relapse risk.

Conclusion
MMX mesalamine was associated with the highest adherence and lowest relapse rates among the four 5-ASA formulations. These findings emphasize the importance of formulation choice in UC management.