Gastroesophageal reflux disease (GERD) is often a chronic disease, with 80% of patients having a relapse of symptoms within one year after treatment withdrawal despite initial healing. The difficulty in maintaining remission is directly related to the extent of the damage before the initial treatment commenced. Due to the preponderance of complications associated with GERD, maintenance therapy with a minimal dose of a drug capable of relieving symptoms and healing the mucosa is an important issue.
The therapeutic options for maintaining remission include “on demand” therapy, continual maintenance therapy, or surgery. “On-demand” therapy has been shown to be a reasonable approach for patients with mild symptoms or mild erosive disease. Its success is dependent upon response to initial therapy; patients who had symptom relief after two weeks of therapy had a better outcome than those who required longer therapy. Regarding starting therapy with a proton pump inhibitor when symptoms occur, omeprazole 20 mg qd has been shown to be more effective than a lower dose of omeprazole (10 mg qd) or ranitidine 150 mg bid.
Maintenance therapy or continuous therapy is more likely to be necessary in patients with esophagitis or complications. A number of agents used alone or in combination with varying dosing regimens have been studied. In a prospective, randomized trial, 175 patients with reflux esophagitis, grade I–III, were randomly assigned to 12 months of one of the following regimens: cisapride 10 mg tid, ranitidine 150 mg tid, omeprazole 20 mg qd, ranitidine plus cisapride, or omeprazole plus cisapride. The results of the study demonstrated that daily omeprazole (80%) alone or in combination with cisapride (89%) was more effective in preventing lesions or symptoms of esophagitis at 12 months than ranitidine alone (49%), cisapride alone (54%), or ranitidine plus cisapride (66%).
In another prospective study, daily omeprazole (20 mg) maintained remission at 12 months in 89% of patients compared to 32% when receiving weekend omeprazole (20 mg on three consecutive days a week) and 25% when receiving daily ranitidine 150 mg bid. Another study showed similar findings when comparing omeprazole 20 mg daily to omeprazole 20 mg on three consecutive days. The patients who remained in endoscopic remission after 6 months were 11% for placebo, 34% for 3 days a week omeprazole and 70% for daily omeprazole.
These studies demonstrate a relationship between the amount of acid suppression and the successful maintenance of healing and symptom control. The levels of acid suppression produced by omeprazole 20 mg daily were sufficient to maintain most of the patients; the few patients who remained relapse-free on weekend omeprazole or daily ranitidine had milder esophagitis, grade II. Therefore, it is important to establish the grade of the esophagitis before determining the maintenance therapy.
In preventing esophagitis, the various proton pump inhibitors have not shown a difference in relative efficacy over a prolonged period. Continuous maintenance therapy with lansoprazole 30 mg showed no statistical difference in endoscopic (grade II-IV) or symptom relapse compared to omeprazole 20 mg daily after 48 weeks. Both treatments demonstrated a similar adverse effect profile. Because proton pump inhibitors are superior to H2 receptor antagonists in preventing the relapse of esophagitis, proton pump inhibitors are the drugs of choice for maintenance treatment of esophagitis.