Supplementary Material for: Gastric Acid Suppression Is Associated with an Increased Risk of Adverse Outcomes in Inflammatory Bowel Disease

Background: The intestinal microbiota may influence inflammatory bowel disease (IBD) activity. Histamine 2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) can alter the intestinal microbiota. The aim of this study was to assess the relationship between H2RAs, PPIs, and IBD-related outcomes. Methods: We conducted a case-control study of IBD patients using the Veterans Health Affairs databases. Cases were defined by their first instance of an IBD-related hospitalization or surgery and the exposure of interest was H2RA or PPI use 30 days prior to the outcome. Incidence density ratios were calculated using conditional logistic regression. Results: In a cohort of 58,459 patients with IBD, we found 4,887 cases and 9,761 controls with ulcerative colitis (UC) and 4,876 cases and 9,745 controls with Crohn disease (CD). Filled prescriptions for H2RAs were associated with an increased risk of IBD-related hospitalization or surgery in CD patients (adjusted incidence density ratio 1.18; 95% CI 1.03-1.34). A similar association was found for PPIs in UC patients (adjusted incidence density ratio 1.11; 95% CI 1.02-1.21) and CD patients (adjusted incidence density ratio 1.12; 95% CI 1.02-1.22). Conclusions: H2RAs and PPIs were associated with a modestly increased risk of IBD-related hospitalization or surgery.