Zuo XY, Chen QQ. Beyond monotherapy by acid suppression: Reshaping the management of refractory gastroesophageal reflux disease. World J Gastroenterol 2026; 32(7): 116425 [DOI: 10.3748/wjg.v32.i7.116425]
Corresponding Author of This Article
Qian-Qian Chen, MD, Professor, Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, China. qian_qian_chen@163.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Editorial
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Feb 21, 2026; 32(7): 116425 Published online Feb 21, 2026. doi: 10.3748/wjg.v32.i7.116425
Beyond monotherapy by acid suppression: Reshaping the management of refractory gastroesophageal reflux disease
Xin-Ye Zuo, Qian-Qian Chen
Xin-Ye Zuo, Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
Qian-Qian Chen, Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
Author contributions: Zuo XY contributed to the statistical analysis and writing of the original manuscript; Chen QQ contributed to the conceptualization and supervision of the manuscript. Both of the authors approved the final version to publish.
Supported by General Program of Municipal Natural Science Foundation of Beijing, No. 7232151.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Qian-Qian Chen, MD, Professor, Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, China. qian_qian_chen@163.com
Received: November 11, 2025 Revised: December 11, 2025 Accepted: December 25, 2025 Published online: February 21, 2026 Processing time: 87 Days and 8.5 Hours
Abstract
Gastroesophageal reflux disease (GERD) is highly prevalent worldwide. Although standard proton pump inhibitor (PPI) or potassium-competitive acid blocker therapy is effective in most patients, some patients develop refractory GERD (rGERD). Previous studies exploring the characteristics and risk factors for rGERD had substantial limitations. A recent multicenter cross-sectional study conducted across 18 medical centers in Shanghai directly compared GERD and rGERD, and identified prolonged disease duration and anxiety as independent high-risk factors for rGERD. Moderate-intensity physical activity for at least 90 minutes/week was found to be a protective factor. The 8-week PPI/potassium-competitive acid blocker therapy is the standard regimen for GERD, whereas adjustments are needed for rGERD, such as switching or increasing the dose of PPIs or using vonoprazan instead. Additionally, endoscopic interventions and surgeries are supplementary options for patients with rGERD. Anti-anxiety interventions, standardized exercise prescriptions, and lifestyle factors such as sleep and weight management should be explored as a “multidimensional risk-targeted intervention” for the management and treatment of rGERD. This multicenter cross-sectional study offers forward-looking findings for rGERD prevention, but has limitations: A single-region sample lacks representativeness, and its cross-sectional design requires long-term randomized controlled trial for causal evidence.
Core Tip: A recent Shanghai study identified prolonged disease duration and anxiety as key risk factors for refractory gastroesophageal reflux disease, whereas moderate physical activity is protective. Management should extend beyond standard acid suppression to include a “multidimensional” strategy incorporating anti-anxiety interventions, exercise prescriptions, and multidisciplinary collaboration. However, the study’s single-region sample and cross-sectional design necessitate future multi-regional, long-term research to validate and establish causality.
