Potassium-competitive Acid Blockers Versus Proton Pump Inhibitors for Erosive Esophagitis: A Systematic Review and Network Meta-analysis

Background/Aims Potassium-competitive acid blockers (P-CABs) have emerged as promising alternatives to proton pump inhibitors (PPIs) to treat erosive esophagitis (EE). This study aims to compare the efficacy and safety of P-CABs and PPIs in patients with mild to severe EE stratified by treatment phase. Methods A systematic literature search was conducted using PubMed, MEDLINE, and the Cochrane Central Register of Controlled Trials. Randomized controlled trials comparing the efficacy of P-CABs and PPIs for EE were included. The pooled risk ratios (RRs) and risk differences with 95% confidence intervals (CIs) were calculated. A frequentist network meta-analysis was performed, and treatment ranking was assessed using P-scores. Results Nineteen studies evaluating 5 P-CABs (vonoprazan, tegoprazan, keverprazan, fexuprazan, and zastaprazan) and 2 PPIs (lansoprazole and esomeprazole) were included. P-CABs demonstrated superior efficacy in healing EE during the initial phase, particularly in patients with severe EE (RR = 1.10; 95% CI, 1.00-1.20) and were also associated with a lower EE recurrence risk during maintenance treatment (RR = 0.59; 95% CI, 0.41-0.85). The efficacy was notably greater in patients with higher EE severity and among cytochrome P450 2C19 extensive metabolizers. The safety profiles of the P-CABs and PPIs were comparable. Vonoprazan consistently ranked the highest for both initial treatment (P-score = 0.68) and maintenance (P-score = 0.94). Conclusions P-CABs, especially vonoprazan, showed superior efficacy compared to PPIs in both the initial and maintenance treatment of EE. These findings support the use of P-CABs as a potent and reliable first-line option for EE management, particularly in high-risk populations, with acceptable safety outcomes.