Prevalence and Risk Factors Associated With Inflammatory Bowel Disease in Patients Using Proton-Pump Inhibitors: A Population-Based Study

Abstract

Background and aim Proton pump inhibitor (PPI) is a heavily prescribed medication in the United States that is used to treat several gastrointestinal disorders. Although it has been considered to be safe compared to other medications, multiple gastrointestinal side effects have been reported. These effects of PPIs might stem from the progressive alteration of the intestinal microbiome. Patients with inflammatory bowel disease (IBD) using PPI are also seen to be less likely to achieve remission. However, in the current literature, there is very little evidence of the risk of developing IBD in patients who have been using PPIs. Therefore, our aim was to perform a cross-sectional population-based study with in-depth analysis to assess the prevalence and risk factors of IBD amongst PPI users in the United States. Methodology A validated multicenter and research platform database of more than 360 hospitals from 26 different healthcare systems across the United States was utilized to construct this study. A cohort of patients with a diagnosis of ulcerative colitis (UC) and Crohn's disease (CD) between 1999-2022 was identified using the Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT). Patients aged 18 to 65 years were included. We excluded any individual who had a diagnosis of chronic liver disease, autoimmune disease (excluding IBD), or cancer. The risk of IBD was calculated using a multivariate regression analysis to account for potential confounders including non-steroidal anti-inflammatory drugs (NSAIDs) use, smoking, patients who have had a diagnosis of alcoholism, gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), and metabolic syndrome. A two-sided P-value <0.05 was considered statistically significant, and all statistical analyses were performed using R version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria, 2008). Results A total of 79,984,328 individuals were screened in the database and 45,586,150 patients were selected in the final analysis after accounting for inclusion and exclusion criteria. Using multivariate regression analysis, the risk of developing UC and CD was calculated. The odds of having UC amongst patients on PPI was 2.02 (95%CI 1.98-2.06), P-value <0.001. Similarly, the odds of having CD were high amongst PPI users (OR 2.79, 95%CI 2.75-2.84), P- value <0.001 Conclusion Our study demonstrates that patients on PPIs are frequently found to have UC and CD even when adjusting for common risk factors. Hence, we urge clinicians to be aware of this association in order to limit unnecessary prescriptions of PPIs, especially for patients who are at risk for autoimmune diseases.

Keywords: crohn’s disease; database; inflammatory bowel disease; population-based study; proton pump inhibitor; ulcerative colitis.