Randomized, multicenter study: on-demand versus continuous maintenance treatment with esomeprazole in patients with non-erosive gastroesophageal reflux disease

Abstract

Background: Most patients with gastroesophageal reflux disease experience symptomatic relapse after stopping acid-suppressive medication. The aim of this study was to compare willingness to continue treatment with esomeprazole on-demand versus continuous maintenance therapy for symptom control in patients with non-erosive reflux disease (NERD) after 6 months.

Methods: This multicenter, open-label, randomized, parallel-group study enrolled adults with NERD who were heartburn-free after 4 weeks' treatment with esomeprazole 20 mg daily. Patients received esomeprazole 20 mg daily continuously or on-demand for 6 months. The primary variable was discontinuation due to unsatisfactory treatment. On-demand treatment was considered non-inferior if the upper limit of the one-sided 95 % confidence interval (CI) for the difference between treatments was <10 %.

Results: Of 877 patients enrolled, 598 were randomized to maintenance treatment (continuous: n = 297; on-demand: n = 301). Discontinuation due to unsatisfactory treatment was 6.3 % for on-demand and 9.8 % for continuous treatment (difference -3.5 % [90 % CI: -7.1 %, 0.2 %]). In total, 82.1 and 86.2 % of patients taking on-demand and continuous therapy, respectively, were satisfied with the treatment of heartburn and regurgitation symptoms, a secondary variable (P = NS). Mean study drug consumption was 0.41 and 0.91 tablets/day, respectively. Overall, 5 % of the on-demand group developed reflux esophagitis versus none in the continuous group (P < 0.0001). The Gastrointestinal Symptom Rating Scale Reflux dimension was also improved for continuous versus on-demand treatment. Esomeprazole was well tolerated.

Conclusions: In terms of willingness to continue treatment, on-demand treatment with esomeprazole 20 mg was non-inferior to continuous maintenance treatment and reduced medication usage in patients with NERD who had achieved symptom control with initial esomeprazole treatment.

Trial registration: ClinicalTrials.gov identifier (NCT number): NCT02670642 ; Date of registration: December 2015.

Keywords: Discontinuation; Esomeprazole; Gastroesophageal reflux disease; Heartburn; Non-erosive reflux disease; On-demand.

Fig. 1

Study design. Abbreviations: NERD, non-erosive reflux disease (without mucosal breaks on pre-treatment endoscopy); od, once daily

Fig. 2

Flow diagram of patients’ disposition through the stages of the study. Abbreviations: ITT, intention-to-treat; PP, per-protocol

Fig. 3

Mean (a) Gastrointestinal Symptom Rating Scale and (b) Quality of Life in Reflux and Dyspepsia questionnaire scores at baseline^a, following 4 weeks’ initial (short-term) treatment with esomeprazole 20 mg once daily, and after maintenance treatment with either on-demand or continuous esomeprazole for 6 months (intention-to-treat population). ^aBaseline corresponds to visit 1 (week −4). *P < 0.01 and **P ≤ 0.001 for the difference in the change in scores from baseline to the end of maintenance treatment for continuous versus on-demand treatment groups