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P-CABs vs PPIs: Best Options for Healing Erosive Esophagitis

Publication Title: Comparative efficacy and safety of potassium-competitive acid blockers and proton pump inhibitors for erosive esophagitis: a network meta-analysis of randomized controlled trials

Summary

Question

This study compared the effectiveness and safety of potassium-competitive acid blockers (P-CABs) and proton pump inhibitors (PPIs) for treating erosive esophagitis (EE), a condition characterized by damage to the esophagus due to stomach acid. The authors aimed to evaluate the healing and recurrence rates of EE over short- and long-term treatment durations.

Why it Matters
EE is a common complication of gastroesophageal reflux disease (GERD) and is often treated with PPIs, which have limitations such as variable effectiveness and the need for specific timing with meals. P-CABs are a newer class of drugs that may provide more consistent acid suppression without such restrictions. Understanding which treatments are most effective and safe could improve patient outcomes, especially for those with severe EE or incomplete responses to standard therapies.
Methods

The researchers conducted a network meta-analysis of 39 randomized controlled trials involving over 27,000 participants. These trials compared various P-CABs, PPIs, and placebo treatments. The analysis focused on healing rates at 4 and 8 weeks, recurrence rates at 24 weeks, and safety outcomes. Data were categorized by severity of EE using the Los Angeles (LA) classification system, with 4 grades from mild (A) to severe (D).

Key Findings

Vonoprazan 20 mg, zastaprazan 20 mg, and esomeprazole 40 mg were the most effective treatments for healing EE at 8 weeks, particularly for severe cases (LA grades C/D). At 24 weeks, vonoprazan (10 mg and 20 mg) and esomeprazole 20 mg were most effective in preventing recurrence. Safety profies were comparable across treatments. However, no studies evaluated twice-daily PPI regimens, a common strategy for patients with persistent symptomatic EE.

Implications

These findings suggest that P-CABs and high-dose esomeprazole are strong options for treating EE, especially in severe cases. Future research should address long-term safety and compare P-CABs with optimized PPI regimens.

Next Steps
The authors recommend further studies to evaluate the long-term safety of P-CABs, including risks related to elevated stomach acid suppression, such as infection and hypergastrinemia (excess gastrin hormone). Comparative trials of P-CABs against twice-daily PPI regimens are also needed to better define their role in clinical practice.
Funding Information
This research was not supported by any external funding. Yale University also provided funding and support for this research.

Full Citation

Al Hayek M, Lucendo A, Barberio B, Yadlapati R, Nounou M, Beshr M, Gyawali C, Chan W, Salama A, Elhadi M, Savarino E, Laine L. Comparative efficacy and safety of potassium-competitive acid blockers and proton pump inhibitors for erosive esophagitis: a network meta-analysis of randomized controlled trials. EClinicalMedicine 2026, 93: 103807. PMID: 41768276, PMCID: PMC12945529, DOI: 10.1016/j.eclinm.2026.103807.
This AI-assisted summary has been reviewed and approved by at least one of the study's authors to ensure it accurately reflects the research.

Authors

  • Mohammad Al Hayek

    First Author
    School Building Streamline Icon: https://streamlinehq.comOther Institution

  • Loren Laine, MD

    Last Author
    Yale School of Medicine

    Professor of Medicine (Digestive Diseases)

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Other Authors

  • Alfredo J Lucendo;
  • Brigida Barberio;
  • Rena Yadlapati;
  • Mohamedhen Vall Nounou;
  • Mohammed S Beshr;
  • C Prakash Gyawali;
  • Walter W Chan;
  • Abdelaziz H Salama;
  • Muhammed Elhadi;
  • Edoardo Vincenzo Savarino

Research Themes

Concepts