New information relevant to long‐term management of endoscopy‐negative reflux disease

Abstract

SUMMARYDespite the fact that the endoscopic appearance of the mucosa is normal in the majority of patients who present with moderate to severe symptoms of acid reflux, valid clinical information on both the natural course of endoscopy‐negative reflux disease and the need for and design of long‐term therapy is still lacking. The aim of this study was to determine the natural course of endoscopy‐negative acid reflux disease over a period of 6 months; to determine whether 10 mg omeprazole once daily is sufficient to control symptoms in patients with symptomatic acid reflux disease, when given either as a strict daily dose or at the discretion of the patient (on‐demand therapy); and to compare the efficacy of 10 and 20 mg omeprazole with that of placebo, in resolving symptoms. A total of 495 patients with endoscopy‐negative acid reflux disease were recruited to compare 10 mg omeprazole daily with placebo, the clinical endpoint being unwillingness to continue in the study due to insufficient symptom control (i.e. heartburn). In a parallel study, 424 patients were randomized, after initial treatment with acid inhibition therapy to maintain symptom control during on‐demand therapy, to 10 or 20 mg omeprazole daily, or placebo. The Psychological General Well‐Being Index was used to compare the quality of life of patients in remission with those suffering a relapse. In the study in which continuous treatment with 10 mg omeprazole daily was compared with placebo, 48% of the patients allocated to placebo were in clinical remission after 6 months compared with 73% of those randomized to omeprazole (P < 0.01). Furthermore, heartburn, the predominant acid reflux symptom, was completely controlled in 80% of omeprazole‐treated patients, compared with 51% of those receiving placebo. In the parallel on‐demand study, 56% of patients allocated to placebo (although consuming significantly more antacids) had adequate symptom control and thus remained in the study for 6 months. In patients receiving either 10 or 20 mg omeprazole daily, 69 and 83%, respectively, experienced adequate symptom control (P = 0.01 and P < 0.01, respectively, compared with placebo). Mean scores on the Psychological General Well‐Being Index of 105.3 ± 2.0 (S.E.M.) were seen in patients in clinical remission, compared with 98.3 ± 2.6 in those experiencing relapse of reflux symptoms (P < 0.05). When studied over a 6‐month period, about half of endoscopy‐negative reflux patients required drug intervention to achieve symptom control. In these patients continuous maintenance therapy with 10 mg omeprazole daily considerably increased the proportion of those experiencing symptom control. Another viable therapeutic strategy in such patients appears to be on‐demand therapy using 20 mg omeprazole.