Achieving Complete Remission in Patients with Erosive Gastroesophageal Reflux Disease (GERD)

Abstract

Purpose: GERD symptoms can persist despite healing and vice versa. We have therefore redefined complete remission as both endoscopically confirmed healing and symptom relief assessed by the validated ReQuest™. Methods: 581 patients with erosive GERD (LA grade A-D) were randomly allocated to once daily treatment with either 40 mg of pantoprazole (PANTO) (n = 288) or esomeprazole (ESO) (n = 293). Treatment was for a maximum of 12 weeks unless complete remission was achieved earlier at 4 or 8 weeks. Esophageal healing was defined as disappearance of all erosive changes. Symptom relief was achieved if the score of the subscale ReQuest™-GI fell below the predefined GERD symptom threshold of 1.725. Complete remission at 12 weeks was the primary variable and at 4 and 8 weeks the secondary ones. The non-inferiority of PANTO vs. ESO was determined by the one-sided 97.5%-Confidence Interval (CI) (Blackwelder method) assuming a non-inferiority margin of -15%. To allow comparison with published reports, endoscopically confirmed healing and symptom relief were also analyzed separately. The efficacy of PANTO and ESO was compared by the two-sided 95% CIs according to the standard normal approximation (non-inferiority margin of -15%). Results: Complete remission per protocol (PP) at 12 weeks was 92.6% for PANTO and 90.2% for ESO (97.5% CI for the difference above −15%: [−2.9%;+∞]). After 12 weeks healing was superior on PANTO (98.0%) than on ESO (94.4%) (CI for the difference above 0 [0.02%;7.27%]; PP); and symptom relief non-inferior: PANTO 94.6% and ESO 91.6% (CI for the difference above -15%[-1.8%;7.9%]; PP). Conclusions: (1) Complete remission is a more realistic indicator of treatment efficacy and gives a different perspective than the traditional approach of assessing healing and symptom relief separately. It shows a higher than expected proportion of patients are inadequately treated after recommended standard therapy of 4–8 weeks (2) PANTO 40 mg proved non-inferior to ESO 40 mg as regards symptom relief but the healing rate was superior.Table: Complete Remission Rates (PP Population)