S835 Comparative Efficacy of Potassium-Competitive Acid Blockers, Proton Pump Inhibitors, and H2-Receptor Antagonists for Healing and Maintenance of Erosive Esophagitis: A Network Meta-Analysis of 164 Randomized Trials

Introduction: Proton pump inhibitors (PPIs) transformed erosive esophagitis (EE) management in the 1990s, largely replacing histamine-2 receptor antagonists (H2RAs) as first-line therapy. Recently, potassium-competitive acid blockers (PCABs) emerged as a novel class of acid-suppression, offering more rapid and sustained acid inhibition, independent of food intake. Although few trials suggest superiority of vonoprazan, a PCAB, over standard-dose lansoprazole for EE healing, comparative data against high-dose or dual-delayed release PPIs remain limited. This network meta-analysis aimed to rank the healing and maintenance of EE with acid suppressants including H2RA, PPI (standard, double, dual-delayed release doses), and PCAB. Methods: Literature search was performed in MEDLINE, Embase, and the Cochrane Library from inception to February 2, 2025. Randomized controlled trials (RCTs) were included if they compared acid-suppressive agents (PCAB, PPI, H2RA) in adults with endoscopically confirmed EE or previously healed EE. Primary outcomes were cumulative healing rates of EE at week 8 and maintenance rates at 6 months. A frequentist network meta-analysis determined risk ratios (RR) with 95% confidence intervals (95% CI), using omeprazole 20 mg once per day and placebo as reference for healing and maintenance outcomes, respectively. Treatments were ranked by P-scores. Sensitivity analyses used vonoprazan 20 mg and 10 mg once per day as alternate references for healing and maintenance. Results: Overall, 164 RCTs evaluated healing (N = 117), maintenance (N = 44), and both (N = 3). For EE healing at week 8, zastaprazan 20 mg once per day (RR 1.17; 95% CI 1.09-1.26; P-score = 0.95), dual-delayed release esomeprazole 40 mg once per day (RR 1.13; 95% CI 1.04-1.23; P-score = 0.88), and dexlansoprazole 90 mg once per day (RR 1.10; 95% CI 1.06-1.15; P-score = 0.84) were most efficacious. H2RAs consistently ranked lowest. Compared to vonoprazan 20 mg once per day, only zastaprazan 20 mg once per day had significantly better healing. For maintenance at 6 months, omeprazole 20 mg 4 times per day (RR 6.51; 95% CI 3.92-10.81; P-score = 1.00), dexlansoprazole 60 mg once per day (RR 3.16; 95% CI 2.59-3.86; P-score = 0.91), and esomeprazole 40 mg once per day (RR 2.87; 95% CI 2.54-3.25; P-score = 0.85) were most effective. At 3 months, omeprazole 20 mg 4 times per day, vonoprazan 20 mg once per day, and lansoprazole 30 mg once per day were top-performing regimens. Conclusion: Zastaprazan 20 mg once per day was most effective agent for EE healing, whereas omeprazole 20 mg 4 times per day best prevents recurrence. Overall, PCABs like vonoprazan do not consistently outperform dual-delayed release or double-dose PPI.