Association between Vonoprazan and the risk of gastric cancer after Helicobacter pylori eradication

Background and Aims Potassium-competitive acid blockers (PCABs) have been increasingly used to treat upper gastrointestinal disorders, replacing proton pump inhibitors (PPIs). While PPIs are associated with an increased risk of gastric cancer (GC) after Helicobacter pylori (Hp) eradication, it is uncertain whether PCABs carry the same risk. Methods Using a population-based claims database in Japan, we identified patients who were prescribed a clarithromycin-based first regimen of Hp eradication between 2015 and 2018. Patients who failed this regimen and those diagnosed with GC before or within one year after Hp eradication were excluded. We compared GC incidence between PCAB users and histamine type-2 receptor antagonist (H2RA) users, matching them based on propensity scores calculated with considerations for age, sex, smoking, alcohol consumption, comorbidities, and co-administered medications. PCABs included only Vonoprazan in this study. Results Among 54055 patients, 568 (1.05%) developed GC during the follow-up period (mean 3.65 years). The cumulative incidence of GC was 1.64% at 3 years, 2.02% at 4 years, and 2.36% at 5 years in PCAB users; 0.71% at 3 years, 1.04% at 4 years, and 1.22% at 5 years in H2RA users. The use of PCABs was associated with a higher GC risk (matched HR 1.92; 95%CI 1.13 to 3.25, P = .016). Longer PCAB use and high-dose PCAB use were significantly associated with a higher incidence of GC. Sensitivity analyses showed the risk of GC incidence among PCAB users was comparable to that of PPI users. Conclusions The use of PCABs was associated with an increased risk of GC among Hp-eradicated patients, with duration/dose response effects.