The effect of proton-pump inhibitor therapy on disease outcomes in inflammatory bowel disease: a population-based cohort study

Background: Proton pump inhibitors (PPIs) use has been linked to adverse outcomes in patients with inflammatory bowel disease (IBD). However, it remains unknown whether this is due to protopathic bias (i.e., when the outcome precedes exposure). Objectives: We aimed to conduct a propensity-weighted study of the association between PPI use and IBD-related hospitalizations and surgery in patients with IBD. Design: Historical propensity score (PS)-weighted cohort study. Methods: We identified all Danish residents diagnosed with IBD in 2000–2022 in the Danish National Patient Registry. We analyzed separate PPI treatment episodes allowing an individual to contribute with more than one PPI episode. We used PS-weighted Cox regression to estimate the hazard ratio (HR) for IBD-related hospitalization and surgery for current PPI-users compared with current nonusers. Results: We identified 50,460 patients with IBD (67% with ulcerative colitis, 33% with Crohn’s disease). Five years after their diagnosis, two-thirds of patients with IBD had used PPI at some point and 10% were in current treatment. The weighted HR for IBD-related hospitalizations was 1.45 (95% confidence interval (CI): 1.38–1.52) during the first year after PPI prescription, and 1.16 (95% CI: 1.05–1.28) thereafter. The weighted HR for IBD-related surgery was 1.21 (95% CI: 1.11–1.32) the first year and 1.35 (95% CI: 1.18–1.54) thereafter. Conclusion: We observed a 20%–40% higher rate of IBD-related hospitalization and surgery, the first year after PPI prescription in patients with IBD which most likely represents a protopathic bias, yet the rate of IBD-related surgery remained elevated more than 1 year after PPI prescription.