Background: In recent years, the prevalence of proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) has been increasing, posing a clinical obstacle to improving the management of GERD patients. The ability of known predictive factors to explain therapeutic response to PPI remains insufficient. Therefore, we examined whether the addition of early therapeutic response to PPI as an explanatory variable may increase the predictive power for PPI-refractory GERD. Methods: The severity and therapeutic response of GERD symptoms to PPI were evaluated using the GastroEsophageal Reflux and Dyspepsia Therapeutic Efficacy and Satisfaction Test (GERD-TEST) questionnaire at baseline and at 2 and 4 weeks after treatment. The relevance of the therapeutic effect of PPI at 2 weeks compared to that at 4 weeks was examined in 301 patients with GERD. Independent predictive factors for refractory GERD at 4 weeks of PPI therapy were examined in 182 patients. The effect of various clinical factors, including the early response to PPI, was assessed using multiple regression analysis. Results: The number of PPI-therapy responders increased significantly with the duration of treatment (p < 0.0001). The response to PPI therapy at 2 weeks was significantly correlated with that at 4 weeks (p < 0.0001). Multiple regression analysis revealed that the therapeutic response to PPI at 2 weeks was by far the strongest predictor of the therapeutic effect at 4 weeks among all clinical factors. Conclusions: Medication change for PPI-refractory GERD at 2 weeks may be an efficacious therapeutic strategy to improve patients’ quality of life.
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