Potassium-competitive acid blockers and proton-pump inhibitors for the healing and maintenance of erosive esophagitis: a comprehensive and updated systematic review with network meta-analysis
Abstract
Randomized controlled trials (RCTs) suggest that potassium-competitive acid blockers (PCABs) are non-inferior to standard-dose proton pump inhibitors (PPIs) for erosive esophagitis (EE). However, direct comparative data against double-dose or dual-delayed release PPIs remain limited. This network meta-analysis (NMA) ranks the efficacy of PCABs and PPIs (standard, double, and dual-delayed-release doses) for EE healing and maintenance. A systematic search of MEDLINE, EMBASE, and the Cochrane Library from inception through February 2, 2025 (updated on December 15, 2025) identified RCTs comparing PCABs or PPIs in adults with endoscopically confirmed EE or previously healed EE. Primary outcomes were EE healing at weeks 4 and 8, and maintenance at 6 months. A frequentist NMA estimated risk ratios (RRs) with 95% confidence intervals (95%CI), using vonoprazan 20 mg once daily (QD) and 10 mg QD as reference for healing and maintenance studies, respectively; ranking metrics (P-scores) were used descriptively. A total of 99 RCTs were included. At week 4, several regimens showed similar healing rate to vonoprazan 20 mg QD, including linaprazan 75 mg BID, linaprazan 50 mg BID, and zastaprazan 20 mg QD. At week 8, zastaprazan 20 mg QD was significantly better than vonoprazan 20 mg QD (RR 1.10; 95%CI 1.01-1.21; P-score = 0.92). For maintenance at 6 months, several standard-dose regimens (including esomeprazole 40 mg QD and vonoprazan 20 mg QD) showed similar efficacy, whereas lower-dose…
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