A Meta-Analysis of Proton Pump Inhibitor Exposure and the Risk of Adverse Outcomes in Patients with Inflammatory Bowel Disease

Introduction: This study aims to investigate the association between proton pump inhibitors (PPIs) exposure and adverse outcomes in patients with inflammatory bowel disease (IBD). Methods: According to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE), we conducted a comprehensive search of PubMed, Web of Science, Embase, and the Cochrane Library databases for relevant cohort and case-control studies comparing the incidence of adverse outcomes between IBD patients exposed to PPIs and those not exposed, from the inception of the databases to April 2024. The primary adverse outcomes analyzed included hospitalization and surgery. Results: Five studies, encompassing nearly 100,000 subjects, were included in this meta-analysis. The findings indicated that IBD patients exposed to PPIs had a significantly higher incidence of adverse outcomes compared to those not exposed (Odds ratio [OR]=1.24, 95%CI=1.07-1.44, p=0.004), although it was low-quality evidence. This increased risk was observed in both ulcerative colitis (UC) (OR=1.38, 95%CI=1.04-1.83, p=0.025) and Crohn's disease (CD) (OR=1.14, 95%CI=1.02-1.29, p=0.025). Additionally, the incidence of surgery was higher in IBD patients with PPI exposure (OR=1.31, 95%CI=1.02-1.68). However, the OR for hospitalization did not show a statistically significant difference (OR=1.43, p=0.244). Moreover, the use of glucocorticoids was more frequent among patients exposed to PPIs (OR=1.16, 95%CI=1.06-1.28, p=0.001). Conclusion: PPI exposure may be associated with an increased risk of adverse outcomes in IBD patients, particularly a higher rate of surgery. Limited by various factors, the evidence is considered low quality.