S986 Four-Week Healing Rates of Erosive Esophagitis: A Network Meta-Analysis of PCABs Versus PPIs

Introduction: Proton pump inhibitors (PPIs) have long been the cornerstone of treatment for erosive esophagitis (EE), but potassium-competitive acid blockers (PCABs) have emerged as a promising alternative with faster onset and longer acid suppression. However, the comparative efficacy of individual PCAB agents remains unclear. This network meta-analysis aimed to evaluate and compare the healing efficacy of various PCABs and PPIs in EE, with subgroup analysis based on Los Angeles (LA) classification. Methods: A systematic search was performed across PubMed, Embase, Scopus, Web of Science, and ClinicalTrials.gov up to May 2025. Randomized controlled trials evaluating healing rates of EE with PCABs versus PPIs were included. The primary outcome was the 4-week healing rate. Patients were stratified based on LA grades A/B versus C/D. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for each agent using a random-effects network meta-analysis model. Results: Twelve trials involving 4,263 patients evaluated 4-week healing rates in erosive esophagitis. Treatments included vonoprazan (32.8%), tegoprazan (9.1%), fexuprazan (5.9%), keverprazan (2.5%), zastaprazan (3.1%), linaprazan (4.2%), and PPIs (42.5%). Most patients (73.2%) had LA grade A or B esophagitis, while 26.8% had grade C or D. Only zastaprazan 20 mg demonstrated a statistically significant improvement in the overall healing rate compared to PPIs (OR 2.75; 95% CI 1.06 to 7.13). However, no statistically significant differences were observed between any of the drug arms and PPIs in patients with LA grade A/B or LA grade C/D esophagitis. Conclusion: Zastaprazan 20 mg showed superior efficacy in the overall 4-week healing rate compared to PPIs, but no clear advantage was seen for any agent within specific LA grade subgroups. These findings suggest that while certain PCABs may offer benefits over PPIs, their efficacy may not significantly differ in early versus advanced erosive esophagitis. Further head-to-head trials are warranted to better define optimal therapeutic choices across different severities of EE.