S1718 Proton Pump Inhibitors Increase Risk of Clostridioides difficile in Patients With Inflammatory Bowel Disease

Introduction: Clostridioides difficile infection (CDI) is associated with significant morbidity. Usage of proton pump inhibitors (PPI) is a known risk factor in developing CDI in the general population. However, data about the risk of CDI among inflammatory bowel disease (IBD) patients who are on PPI are limited. In this study, we aim to assess this relationship using a large international database. Methods: We conducted a retrospective cohort study using TriNetX, a global multi-institutional federated research database, on adults (≥18 years) diagnosed with IBD over a 20-year period from January 2005 to December 2024 and were prescribed PPIs within the first 6 months from diagnosis. To control for confounders, 1:1 propensity score matching was performed based on age, sex, and race. Our primary outcome of interest was a diagnosis of CDI within 1 year of initiating PPIs. Subgroup analysis was performed for those who had a diagnosis of ulcerative colitis (UC) or Crohn’s disease (CD) separately. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated. Results: We identified 528,121 patients with IBD, of whom 115,132 (5.51%) were exposed to PPI therapy. Patients with PPI use were older (mean age 50.5 vs 46 years; P < 0.001) and included more White (70.71% vs 63.56; P < 0.001) and female (51.94% vs 51.17; P < 0.001) patients when compared to non-PPI users. Propensity score matching resulted in 115,132 patients in each group. IBD patients who were exposed to PPI had a significantly higher risk for CDI when compared to no PPI use (aOR 2.95, 95% CI 2.69-3.22). Similarly, risk of CDI increased in PPI users among UC (aOR 2.69, 95% CI 2.37-3.02) and CD (aOR 3.46, 95% CI 3.02-4.03) patients compared to non-PPI users. Conclusion: Our study showed that PPI use in patients with IBD increases the risk for developing CDI within 1 year by 3-folds when compared to non-PPI users. Similar trends were observed when stratifying patients by their IBD phenotype. PPI use in IBD patients should be reserved for clear clinical indications to minimize the risk of CDI.