Gong EJ, Bang CS, Lee JJ, Baik GH. Comparative efficacy and pharmacological heterogeneity of individual potassium-competitive acid blockers: A systematic review and network meta-analysis. World J Gastroenterol 2026; 32(39): 121372 [DOI: 10.3748/wjg.121372]
Corresponding Author of This Article
Chang Seok Bang, MD, PhD, Department of Internal Medicine, Hallym University College of Medicine, Sakju-ro 77, Chuncheon 24253, Gangwon-do, South Korea. cloudslove@naver.com
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Gastroenterology & Hepatology
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Gong EJ, Bang CS, Lee JJ, Baik GH. Comparative efficacy and pharmacological heterogeneity of individual potassium-competitive acid blockers: A systematic review and network meta-analysis. World J Gastroenterol 2026; 32(39): 121372 [DOI: 10.3748/wjg.121372]
World J Gastroenterol. Oct 21, 2026; 32(39): 121372 Published online Oct 21, 2026. doi: 10.3748/wjg.121372
Comparative efficacy and pharmacological heterogeneity of individual potassium-competitive acid blockers: A systematic review and network meta-analysis
Eun Jeong Gong, Chang Seok Bang, Jae Jun Lee, Gwang Ho Baik
Eun Jeong Gong, Chang Seok Bang, Department of Internal Medicine, Hallym University College of Medicine, Chuncheon 24253, Gangwon-do, South Korea
Jae Jun Lee, Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon 24253, Gangwon-do, South Korea
Gwang Ho Baik, Department of Gastroenterology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon 24253, Gangwon-do, South Korea
Co-corresponding authors: Chang Seok Bang and Jae Jun Lee.
Author contributions: Gong EJ and Bang CS were responsible for writing-original draft; Bang CS was responsible for conceptualization, formal analysis, methodology, project administration, and resources; Bang CS and Lee JJ were responsible for writing-review and editing as co-corresponding authors; Gong EJ, Bang CS, Lee JJ, and Baik GH were responsible for data curation, investigation; Lee JJ was responsible for funding acquisition.
AI contribution statement: After all point-by-point responses were written, the English proofreading was performed by the LLM. This was done by Grammarly and Gemini.
Supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT), No. RS-2023-00223501.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Corresponding author: Chang Seok Bang, MD, PhD, Department of Internal Medicine, Hallym University College of Medicine, Sakju-ro 77, Chuncheon 24253, Gangwon-do, South Korea. cloudslove@naver.com
Received: March 24, 2026 Revised: April 17, 2026 Accepted: June 5, 2026 Published online: October 21, 2026 Processing time: 167 Days and 0.8 Hours
Abstract
BACKGROUND
Vonoprazan consistently demonstrates superior Helicobacter pylori eradication (HPE) rates compared to other potassium-competitive acid blockers (P-CABs), yet the pharmacological basis for this heterogeneity remains unclear. We hypothesized that the acid dissociation constant (pKa) – which determines acid stability and parietal cell accumulation – may explain the differential efficacy among individual P-CABs.
AIM
To examine whether pKa values predict clinical efficacy of P-CABs for HPE and erosive esophagitis healing.
METHODS
A systematic review and network meta-analysis were conducted. Randomized controlled trials (RCTs) comparing P-CABs with proton pump inhibitors (PPIs) were identified from core databases (up to January 2026). Risk of bias was assessed using RoB 2.0 and certainty of evidence using GRADE.
RESULTS
Thirty RCTs (7639 patients) were included for HPE. High-pKa P-CABs (vonoprazan of 9.06, keverprazan of 9.12) achieved 82%-84% eradication in clarithromycin-resistant infections vs 32%-40% with PPIs, while low-pKa P-CAB achieved only 47.8% (not significant vs PPI). For erosive esophagitis (10 RCTs; 4196 patients), high-pKa zastaprazan (9.95) achieved 100% Los Angeles classification grade C/D healing vs 83.3% with esomeprazole, whereas low-pKa P-CABs showed inferior outcomes. Spearman correlation analysis revealed a positive association between pKa and efficacy (ρ = 0.80). However, fexuprazan (pKa of 9.04) showed PPI-equivalent outcomes despite high-pKa, highlighting pKa as necessary but not sufficient for clinical efficacy. Network ranking confirmed high-pKa P-CABs as top-ranked agents. No publication bias was detected.
CONCLUSION
P-CAB efficacy may not be uniform across the class. High-pKa P-CABs (≥ 9.0) were associated with higher eradication rates in clarithromycin-resistant infections and superior healing in severe esophagitis, whereas low-pKa P-CABs showed limited advantages over PPIs. The pKa may serve as a hypothesis-generating pharmacological parameter, though all P-CAB comparisons were indirect and prospective validation is needed.
Core Tip: Potassium-competitive acid blockers (P-CABs) suppress acid faster and more consistently than proton pump inhibitors. Over 30 meta-analyses pooled all P-CABs as a single class. Guidelines treat individual P-CABs as interchangeable. Individual P-CABs differ substantially in clinical outcomes, suggesting that efficacy may not be uniform across the class. Acid dissociation constant (pKa) values showed a positive correlation with clinical efficacy, with high-pKa P-CABs (vonoprazan, keverprazan) achieving 82%-84% eradication in clarithromycin-resistant Helicobacter pylori vs 47.8% for low-pKa tegoprazan. However, fexuprazan (pKa of 9.04) did not follow this pattern, demonstrating that pKa alone is insufficient to predict outcomes. The pKa may be one contributing factor but is not sufficient alone. Multiple pharmacological properties likely contribute to antisecretory effectiveness and clinical outcomes. These findings generate the hypothesis that pKa may inform P-CAB selection, particularly for clarithromycin-resistant infection and severe esophagitis, pending prospective validation.
