Comparative efficacy and pharmacological heterogeneity of individual potassium-competitive acid blockers: A systematic review and network meta-analysis

Figure 4 Forest plot of network meta-analysis comparing potassium-competitive acid blockers vs proton pump inhibitors for 8-week erosive esophagitis healing. Each row represents a randomized controlled trial, with squares indicating point estimates of odds ratio and horizontal lines representing 95%CIs. Diamond at the bottom shows the pooled effect estimate. Ten randomized controlled trials comparing five potassium-competitive acid blockers [vonoprazan, tegoprazan, fexuprazan (FXP), keverprazan, zastaprazan] with proton pump inhibitors (PPIs) for erosive esophagitis healing are shown. High-acid dissociation constant (pKa) potassium-competitive acid blockers demonstrated significant superiority, while tegoprazan (pKa of 5.1) and FXP (pKa of 9.04, the “FXP paradox”) showed no significant advantage over PPIs. Overall healing rates were high across all treatments (91%-99%), with ceiling effects limiting differentiation in mild-to-moderate esophagitis. Notably, FXP (pKa of 9.04) showed no significant advantage over PPIs (odds ratio = 0.95) despite high-pKa, illustrating the FXP paradox. P-CAB: Potassium-competitive acid blocker; PPI: Proton pump inhibitor.