Factors affecting response to proton pump inhibitor therapy in patients with gastroesophageal reflux disease: a multicenter prospective observational study

Background: Proton pump inhibitor (PPI) therapy, the first-line treatment for gastroesophageal reflux disease (GERD), is not always effective. This study aimed to examine the effect of pretreatment patient characteristics on response to PPI therapy. Methods: Japanese outpatients with symptomatic GERD scheduled to receive endoscopy and PPI therapy were enrolled in this multicenter prospective observational study. The patients’ characteristics, including GERD and dyspeptic symptoms, anxiety, depression, and quality of life, were assessed using questionnaires before and 2 and 4 weeks after the start of PPI therapy. Factors affecting therapeutic response were examined by simple and multiple regression analyses using three patient-reported outcome measures as objective variables. Results: Data from 182 patients were analyzed. In multiple regression analysis using the residual symptom rate as an objective variable, lower GERD symptom score (p < 0.05), absence of erosive esophagitis (p < 0.05), higher epigastric pain/burning symptom score (p < 0.05), and higher depression subscale score (p < 0.05) accompanied poorer therapeutic response. In analyses using the patient’s impression of therapy, lower GERD symptom score (p < 0.05) and absence of erosive esophagitis (p < 0.05) accompanied poorer therapeutic response. In analyses using the relative GERD symptom intensity evaluated using a numeric rating scale, lower GERD symptom score (p < 0.05), higher epigastric pain/burning symptom score (p < 0.1), and lower body mass index (p < 0.05) accompanied poorer therapeutic response. Conclusions: Patients who complained of milder GERD symptoms before treatment were likely to have poorer response to PPI therapy. Association of absence of erosive esophagitis, severer epigastric pain/burning symptoms, lower body mass index, and severer depression with poorer therapeutic response was also suggested.