Beyond monotherapy by acid suppression: Reshaping the management of refractory gastroesophageal reflux disease

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.