P4893 - Second Generation Potassium-Competitive Acid Blockers Match Proton Pump Inhibitors in Healing and Safety for Erosive Esophagitis: A Systematic Review and Meta-Analysis of Four Double-Blind, Randomized Controlled Trials

Ashesh Das, MBBS¹, Venkata Dileep Kumar Veldi, MBBS², Urvashi Bharia, ³, Harshawardhan Dhanraj Ramteke, MBBS⁴, Rakhshanda Khan, MBBS⁵, Rishi Chowdhary, MD⁶, Heer Pareshbhai Shah, MBBS⁷, Syeda Ayesha Fatima, MBBS⁸, Tanisha Vinod, ⁹, Akif Shahid. Khan, MBBS¹⁰, Shankar Biswas, MD¹¹, Wong Khai. Hsin, MBBS¹², Sagar K. Patel, MBBS¹³, Riyakumari B. Patel, MBBS¹⁴
1KPC Medical College and Hospital , Kolkata, India, Kolkata, West Bengal, India; 2Gayatri Vidya Parishad Institute of Health care and Medical Technology, Visakhapatnam, Andhra Pradesh, India; 3Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai, Navi Mumbai, Maharashtra, India; 4Anhui Medical University, Hefei, Hefei, Anhui, China; 5Ayaan institute of medical sciences, Moinabad, Telangana, India; 6Case Western Reserve University / MetroHealth, Cleveland, OH; 7Smt. NHL Municipal Medical College, Ahmedabad, Gujarat, India; 8Shadan Institute of Medical Sciences, Hyderabad, Telangana, India; 9Manipal University College Malaysia, Malacca, Melaka, Malaysia; 10Northwest School of Medicine, Nowshera, North-West Frontier, Pakistan; 11Ivano-Frankivsk National Medical University, Ukraine, Meerut, Uttar Pradesh, India; 12Universiti Malaya, Cyberjaya, Selangor, Malaysia; 13Gujarat Adani Institute of Medical Sciences, Kheda, Gujarat, India; 14Surat Municipal Institute of Medical Education and Research, McKees Rocks, PA

Introduction: Proton-pump inhibitors (PPIs) remain first-line therapy for erosive oesophagitis (EO), yet incomplete acid control and nocturnal breakthrough limit their effectiveness in up to one-third of patients. Second-generation potassium-competitive acid blockers (P-CABs)—notably Tegoprazan and Fexuprazan—provide faster, meal-independent and more durable pH elevation than the first-in-class agent Vonoprazan. Despite their rapidly expanding clinical use, to our knowledge head-to-head performance against PPIs in double-blind RCTs has never been analyzed.

Methods: A systematic search of PubMed, Embase, Scopus, and Cochrane Library identified four double blind RCTs comparing second generation PCABs and PPIs for treatment of EO through May 2025. Data were analysed using RevMan 4.2.1. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using Mantel-Haenszel methods. Random- or fixed-effects models were applied based on heterogeneity (Higgins’ I²). Statistical significance was set at p < 0.05. Risk of bias was assessed using RoB 2.0.

Results: Four double-blind RCTs comprising 1,085 patients with erosive oesophagitis (PPI = 543; P-CAB = 542) met eligibility. The efficacy endpoint showed Endoscopic healing at 4 weeks was achieved in 83 % of PPI‐treated vs 87 % of P-CAB–treated participants (421/505 vs 448/514; RR 0.96, 95 % CI 0.91–1.01; I² = 0 %), and at 8 weeks in 93 % vs 95 % (478/512 vs 490/518; RR 0.99, 95 % CI 0.96–1.02; I² = 0 %). The Safety endpoint showed treatment-emergent adverse events occurred in 31 % of PPI and 28 % of P-CAB recipients (171/543 vs 156/549; RR 1.11, 95 % CI 0.93–1.32; I² = 0 %). Serious adverse events were rare (0.6 % vs 0.4 %; RR 1.42, 95 % CI 0.28–7.17; I² = 28 %), as were withdrawals due to adverse events (1.5 % vs 0.9 %; RR 1.52, 95 % CI 0.55–4.25; I² = 8 %).

Discussion: Second-generation P-CABs matched PPIs for endoscopic healing at 4 and 8 weeks, demonstrating non-inferiority during mucosal repair. Adverse, withdrawal, and serious-event rates were low and similar across groups, confirming a favorable safety profile despite potent acid suppression. Negligible heterogeneity across diverse geographies, molecules, and designs strengthens these findings. Clinically, P-CABs offer a rapid-relief alternative for PPI-refractory patients and may streamline on-demand regimens. Longer-term studies and real-world surveillance are needed to assess sustained efficacy, cost-effectiveness, and any class-specific benefits beyond eight weeks.


Figure: Forest Plots comparing Efficacy and Safety Endpoints of PPIs and 2nd Generation PCABs - in the following order - Endoscopic healing at 4 weeks , Endoscopic Healing at 8 weeks, Treatment Emergent Adverse Events, Serious Adverse Events, Withdrawal due to Adverse Events


Figure: Prisma Flowchart

Disclosures:
Ashesh Das indicated no relevant financial relationships.
Venkata Dileep Kumar Veldi indicated no relevant financial relationships.
Urvashi Bharia indicated no relevant financial relationships.
Harshawardhan Dhanraj Ramteke indicated no relevant financial relationships.
Rakhshanda Khan indicated no relevant financial relationships.
Rishi Chowdhary indicated no relevant financial relationships.
Heer Pareshbhai Shah indicated no relevant financial relationships.
Syeda Ayesha Fatima indicated no relevant financial relationships.
Tanisha Vinod indicated no relevant financial relationships.
Akif Khan indicated no relevant financial relationships.
Shankar Biswas indicated no relevant financial relationships.
Wong Hsin indicated no relevant financial relationships.
Sagar Patel indicated no relevant financial relationships.
Riyakumari Patel indicated no relevant financial relationships.

Ashesh Das, MBBS¹, Venkata Dileep Kumar Veldi, MBBS², Urvashi Bharia, ³, Harshawardhan Dhanraj Ramteke, MBBS⁴, Rakhshanda Khan, MBBS⁵, Rishi Chowdhary, MD⁶, Heer Pareshbhai Shah, MBBS⁷, Syeda Ayesha Fatima, MBBS⁸, Tanisha Vinod, ⁹, Akif Shahid. Khan, MBBS¹⁰, Shankar Biswas, MD¹¹, Wong Khai. Hsin, MBBS¹², Sagar K. Patel, MBBS¹³, Riyakumari B. Patel, MBBS¹⁴. P4893 - Second Generation Potassium-Competitive Acid Blockers Match Proton Pump Inhibitors in Healing and Safety for Erosive Esophagitis: A Systematic Review and Meta-Analysis of Four Double-Blind, Randomized Controlled Trials, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.