LAUSR

BACKGROUND & AIMS For decades, proton pump inhibitors (PPIs) have been the mainstay of treatment for erosive esophagitis. The potassium-competitive acid blocker vonoprazan provides more potent acid inhibition than PPIs but data on its efficacy for erosive esophagitis are limited. METHODS Adults with erosive esophagitis were randomized to once-daily vonoprazan 20mg or lansoprazole 30mg for up to 8 weeks. Patients with healing were re-randomized to once-daily vonoprazan 10mg, vonoprazan 20mg, or lansoprazole 15mg for 24 weeks. Primary endpoints, percentage with healing by week-8 endoscopy and maintenance of healing at week-24 endoscopy, were assessed in non-inferiority comparisons (non-inferiority margins=10%), with superiority analyses pre-specified if non-inferiority was demonstrated. Analyses of primary and secondary endpoints were performed using fixed-sequence testing procedures. RESULTS Among 1024 patients in the healing phase, vonoprazan was non-inferior to lansoprazole in primary analysis and superior on exploratory analysis of healing (92.9 vs. 84.6%; difference=8.3%, 95% CI 4.5-12.2%). Secondary analyses showed vonoprazan non-inferior in heartburn-free days (difference=2.7%, -1.6-7.0%), and superior in healing Grade C/D esophagitis at week 2 (difference=17.6%, 7.4-27.4%). Among 878 patients in maintenance phase, vonoprazan was non-inferior to lansoprazole in primary analysis and superior on secondary analysis of maintenance of healing (20mg vs. lansoprazole difference=8.7%, 1.8-15.5%; 10mg vs. lansoprazole difference=7.2%, 0.2-14.1%) and secondary analysis of maintenance of healing Grade C/D esophagitis (20mg vs. lansoprazole difference=15.7%, 2.5-28.4%; 10mg vs. lansoprazole difference=13.3%, 0.02-26.1%). CONCLUSIONS Vonoprazan was non-inferior and superior to the PPI lansoprazole in healing and maintenance of healing of erosive esophagitis. This benefit was seen predominantly in more severe erosive esophagitis. (ClinicalTrials.gov:NCT04124926).