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

Figure 5 The acid dissociation constant-efficacy relationship among potassium-competitive acid blockers. A: Scatter plot of acid dissociation constant (pKa) vs pooled odds ratio (OR) for Helicobacter pylori eradication [n = 4 potassium-competitive acid blockers (P-CABs), Spearman ρ = 0.80, P = 0.20]; B: Scatter plot of pKa vs pooled OR for erosive esophagitis healing (n = 5 P-CABs, Spearman ρ = 0.80, P = 0.104). In both panels, fexuprazan (FXP) (pKa of 9.04) is highlighted as an outlier with proton pump inhibitor-equivalent efficacy despite high-pKa; C: Individual P-CAB efficacy for erosive esophagitis ordered by pKa, illustrating the FXP paradox: Despite pKa of 9.04, FXP shows OR < 1.0. Dashed line represents ordinary least squares linear regression fit. Error bars represent 95%CIs of pooled ORs. A positive pKa-efficacy trend is observed, but FXP (pKa of 9.04) represents a notable outlier with proton pump inhibitor-equivalent outcomes despite high-pKa. OR: Odds ratio; P-CAB: Potassium-competitive acid blocker; pKa: Acid dissociation constant; PPI: Proton pump inhibitor; TPZ: Tegoprazan; FXP: Fexuprazan; VPZ: Vonoprazan; KVP: Keverprazan; ZPZ: Zastaprazan.