• Tenzin Choden, Hui Zhang, and Atsushi Sakuraba.
• Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA.
• Ann. Med. 2023 Dec 1; 55 (1): 21987752198775.

ObjectiveProton pump inhibitor (PPI) use has been associated with reduced diversity of the gut microbiome and may lead to worse clinical outcomes in inflammatory bowel disease (IBD). We aimed to evaluate whether PPI use affects clinical outcomes in a real-world setting.DesignHealthcare claims data of adult IBD patients were obtained from the IBM MarketScan Database. Multivariable analysis and propensity score-matched analysis were performed to assess associations between PPI use and new biologic start, and IBD-related hospitalizations and surgeries.ResultsA total of 46,234 IBD patients were identified (6,488 (14%) and 39,746 (86%) patients with and without PPI, respectively). Patients on PPI were more likely to be older, female, and smokers and less likely to be on immunomodulators. Multivariable analyses demonstrated that PPI use was associated with new biologic start (odds ratio (OR) 1.11, 95% confidence interval (CI) 1.04-1.18), and IBD-related admissions (OR 1.95, 95% CI 1.74-2.19) and surgeries (OR 1.46, 95% CI 1.26-1.71). Following propensity score matching, patients on PPI remained more likely to start a new biologic (23% vs 21%, p = 0.011), and have IBD-related admissions (8% vs 4%, p < 0.001) and surgeries (4% vs 2%, p < 0.001). Subgroup analyses stratified by age, smoking, and glucocorticoid use showed similar results. There was a dose-response relationship between the number of PPI prescriptions and the risk of new biologic use (p < 0.001) and IBD-related admissions (p < 0.001).ConclusionPPI use was associated with worse clinical outcomes in patients with IBD in the real-world setting. Further studies are warranted to validate these findings, but caution may be needed when prescribing a PPI to IBD patients.Study highlights WHAT IS KNOWNProton pump inhibitors (PPIs) are one of the most prescribed therapies in the United States (US).Reduction of gastric acid secretion by PPI use increases the risk of imbalance in gut microbiota composition and may increase the risk of enteric infections.Recent studies have reported that the use of PPI was associated with development of inflammatory bowel disease (IBD) and reduced rates of remission in patients on infliximab therapy, which may be due to alterations of intestinal microbiota.WHAT IS NEW HEREIn a large real-world US healthcare database study, IBD patients with PPI use were more likely to have a new biologic medication started, have an IBD-related surgery, and have an IBD-related hospitalization, which remained significant after adjusting for confounders by multivariable analysis, propensity-score matched analysis, and subgroup analysis.Appropriate clinical review of PPI necessity may need to be performed in patients with IBD when considering prescribing a PPI or who are already on PPI therapy.

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