Short‐Term Daily Vonoprazan Treatment Is More Commonly Associated With Infectious Gastroenteritis Than Short‐Term Daily PPI Treatment

BACKGROUND: Proton pump inhibitors (PPIs) are linked to various short-term and long-term side effects. Vonoprazan, a potassium-competitive acid blocker, was recently introduced into the US market. This study aims to compare the reported short-term adverse effects of PPIs versus vonoprazan. METHODS: Using TriNetX, we identified a global cohort from 14 countries of first-time vonoprazan or PPI users after November 1, 2023. Vonoprazan users could not have been on a PPI for at least 6 months before initiation. PPI users could not have used vonoprazan. Groups were matched for demographics, comorbidities, and medication use. Kaplan-Meier and Cox proportional hazards models estimated complication risks within 90 days. RESULTS: After propensity score matching, 11,851 patients were included in both cohorts, with average follow-up of 66 days in the vonoprazan group and 60 days in the PPI group. Mean age was 62.3 ± 17.5 years and 62.9 ± 17.7 years, respectively, and most patients were female (58.7% vs. 60.3%, respectively). Within 90 days, vonoprazan users in the global cohort had a higher risk of infectious gastroenteritis than PPI users (HR 2.06; 95% CI 1.37-3.10). In GERD patients, vonoprazan users were at higher risk of infectious gastroenteritis than PPI users (HR 3.00; 95% CI 1.64-5.48), while US-only patients had insufficient number of cases for the comparison. No differences were observed for pneumonia, iron deficiency, and B12 deficiency between both groups. CONCLUSION: Vonoprazan was associated with an increased risk of infectious gastroenteritis within 90 days after drug initiation compared to PPIs.