Association of Proton Pump Inhibitor and Potassium‐Competitive Acid Blocker Use With Discontinuation and Intolerance of Oral 5‐Aminosalicylic Acid in Patients With Ulcerative Colitis

ABSTRACT Aims Proton pump inhibitors (PPIs) and potassium‐competitive acid blockers (PCABs) are widely used for acid‐related disorders. Recent studies have raised concerns that acid suppression may alter gut microbiota and drug pharmacokinetics, potentially influencing therapeutic outcomes in patients with inflammatory bowel disease. However, the impact of PPI/PCAB use on oral 5‐aminosalicylic acid (5‐ASA) therapy and intolerance in ulcerative colitis (UC) remains unclear. We aimed to examine whether concomitant PPI/PCAB use was associated with 5‐ASA discontinuation and intolerance in patients with UC. Methods We retrospectively analyzed consecutive patients who received oral 5‐ASA for the first time between 2015 and 2022 at a single tertiary center. Patients receiving concomitant steroids or cytapheresis at baseline were excluded. The primary outcome was the association between PPI/PCAB use and 5‐ASA intolerance, and the secondary outcome was the association with treatment discontinuation. Results A total of 181 patients were included in this study. The cumulative continuation rates of oral 5‐ASA at 1, 3, and 5 years were 60.4%, 45.4%, and 39.3%, respectively. Overall, 29 patients (16.0%) developed 5‐ASA intolerance. In multivariate analyses, concomitant PPI/PCAB use was independently associated with 5‐ASA intolerance (OR 9.65, 95% CI 1.92–48.5, p < 0.01) and treatment discontinuation (HR 2.46, 95% CI 1.06–5.65, p = 0.034), whereas age ≥ 40 years was associated with lower odds of intolerance. Conclusion Concomitant PPI/PCAB use was associated with higher rates of 5‐ASA discontinuation and intolerance in patients with UC. These findings suggest novel associations and warrant validation in larger, prospective cohorts.