Effects of pantoprazole 20 mg in mild gastroesophageal reflux disease: Once-daily treatment in the acute phase, and comparison of on-demand versus continuous treatment in the long term

Background: Gastroesophageal reflux disease (GERD) is a chronic disorder, and although effective short-term treatment strategies are known, the rate of relapse within 1 year is as high as 90% despite successful acute treatment. Consequently, most patients with GERD require an effective long-term management strategy to achieve adequate symptom control and maintain mucosal healing. Objective: The present study was undertaken to compare the control of GERD symptoms during long-term (24-week) treatment with pantoprazole 20 mg used on-demand or continuously in patients with mild GERD after complete relief of acute GERD symptoms. Methods: Patients with endoscopically confirmed Savary/Miller grade 0 (normal mucosa) or I (patchy red lesions without white coating or with central white coating) GERD were enrolled in this multinational, multicenter study comprising 2 phases. In the first phase, which was open label, patients were treated with pantoprazole 20 mg QD for 4 weeks. The presence and intensity of the symptoms of heartburn, acid regurgitation, and pain on swallowing were assessed. In the second phase, which was an open-label, 24-week, randomized design, only patients completely free of GERD symptoms after acute treatment were included. During this phase, on-demand treatment with pantoprazole 20 mg was directly compared with continuous treatment. The rate of failure to control GERD symptoms after 24 weeks of treatment was estimated using the Kaplan Meier method. Subsequently, the difference between treatments (on-demand minus continuous) and its 95% Cl were calculated, and the on-demand treatment was tested for noninferiority using a predefined noninferiority margin of 20%. The mean daily symptom loads were compared between the treatment groups using the I-sided Wilcoxon rank sum test on a 5% alpha level. The point estimate of the difference was determined using the Hodges-Lehman estimator and the 1-sided 95% CI according to Moses. The number of patients unwilling to continue due to insufficient control of heartburn, acid regurgitation, and pain on swallowing was analyzed using the Kaplan-Meier (time-to-event) analysis. Analysis was performed in the same manner as for the rate of failure to control GERD symptoms, but the 95% Cl was interpreted for statistical superiority. Results: A total of 558 patients were enrolled in this study. At the end of the acute phase, 82. 1 % of patients in the per-protocol (PP) population and 79. 1 % in the intent-to-treat (ITT) population were relieved of all GERD symptoms, and subsequently entered the long-term phase. After 24 weeks of treatment, analysis of the failure rates revealed that on-demand treatment was noninferior to continuous treatment because the 95% Cl was completely below 20% OTT, 12.1% difference [95% Cl, -infinity to 18.9%]; PP, 10.1% difference [95% Cl, -infinity to 17.7%]). The higher perceived mean (SD) daily symptom load in the on-demand group (ITT, 1.26 [1.49] vs 0.82 [1.341) was balanced by the reduced tablet intake in that group (PP, 0.51 [0.31] vs 0.97 [0.11] tablets/d; P < 0.001). With respect to the rate of patients unwilling to continue treatment, no statistically significant difference was observed between the on-demand and continuous groups (ITT/ PP, 0.95/1.13 vs 0.95/1.26). \ Conclusions: In this study of pantoprazole 20 mg tablets in patients with mild GERD, patients receiving on-demand treatment benefited despite their higher symptom load. The similar rates of unwillingness to continue treatment in both groups might suggest that patients were satisfied with the on-demand treatment strategy. On-demand treatment with pantoprazole 20 mg was found to be noninferior compared with continuous therapy with regard to symptom control. Both on-demand and continuous treatments were well tolerated.