Relationship between esomeprazole dose and timing to heartburn resolution in selected patients with gastroesophageal reflux disease

Roy C Orlando¹, Sherry Liu², Marta Illueca³

¹Department of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA, ²Department of Statistics and Informatics, ³Department of Clinical Development, AstraZeneca LP, Wilmington, DE, USA

Objective: To increase response rates to therapy by increasing the dosage of proton pump inhibitor (PPI) therapy in patients with gastroesophageal reflux disease (GERD) whose symptoms are predominantly associated with acid reflux.

Methods: In this double-blind, randomized, proof-of-concept study, 369 patients with GERD and moderate heartburn lasting ≥three days/week, a history of response to antacids/acid suppression therapy, and a positive esophageal acid perfusion test result were randomized to esomeprazole 20 or 40 mg once daily, or to 40 mg twice daily for four weeks. Heartburn symptom relief/resolution was subsequently evaluated.

Results: In this study population, no relationship was apparent between esomeprazole dosage and efficacy variables for sustained heartburn resolution (seven days without symptoms) at week 4 (48.0%, 44.0%, and 41.4% for esomeprazole 20 mg once daily, 40 mg once daily, and 40 mg twice daily, respectively). Nocturnal heartburn resolution with esomeprazole 40 mg twice daily showed a numeric improvement trend versus esomeprazole 20 and 40 mg once daily, but this was not statistically significant.

Conclusions: Heartburn resolution rates at four weeks were similar for all esomeprazole dosages and comparable with rates reported previously, suggesting a plateau effect in terms of clinical response to acid suppression with PPI therapy in this population of selected GERD patients.

Keywords: acid suppressive therapy, GERD, proton pump inhibitor