Duodenal ulcer is a chronic disease with a high risk of relapse -if left untreated, the relapse rate is 50-80% per year (1). However, the relapse rate can be effectively reduced by inhibition of gastric acid secretion. Although many patients can be managed with episodic therapy, controlled either by the patient or doctor, continuous maintenance treatment is often necessary for patients with severe forms of the disease and those at risk of complications (2). Maintenance therapy with single night-time doses of an Hreceptor antagonist reduces relapse rates from approximately 75% to 25% per year (3). As omeprazole is more effective than the H2-receptor antagonists in the acute treatment of duodenal ulcer, healing virtually all patients within 4 weeks (4), it may also be more effective in the maintenance treatment of duodenal ulcer disease. To date, three studies have reported the effect of omeprazole on relapse rates of duodenal ulcer. A Danish multicentre study involved 195 patients, who were treated with omeprazole, either 10 mg once daily, or 20 mg once daily on Friday, Saturday and Sunday (weekend therapy), or with placebo (5). After 6 months, the remission rates were 67% and 70% respectively, for those patients receiving omeprazole -significantly higher than in those receiving placebo (17% after 6 months). An Italian multicentre study of 81 patients found that omeprazole, both 10 mg once daily, and 20 mg once daily at weekends (Friday, Saturday and Sunday), was equally effective in preventing relapse. The proportions of patients in remission were 81% and 70% respectively, after 6 months (6). A multicentre study conducted in South-East Asia recruited 60 patients to receive maintenance therapy with omeprazole, 20 mg once daily, and 63 patients to receive maintenance therapy with placebo (7). Of the 52 patients completing omeprazole therapy, 94% remained in remission after 1 year, compared with 8.5% of the 59 patients remaining in the placebo group -a highly significant difference (p < 0.0001). These studies showed that maintenance therapy with omeprazole is effective, but they did not include comparisons with standard maintenance doses of H,-receptor antagonists (e.g. ranitidine, 150 mg nocte). Therefore, a large multicentre study, covering 16 countries, was started in November 1989 to compare the effects of omeprazole, 10 or 20 mg once daily, with ranitidine, 150 mg nocte, over 1 year. Patients recruited to the study were aged 18-80 years, with a duodenal ulcer at least 5 mm in diameter. Following healing with omeprazole, 20 or 40 mg daity for 2-8 weeks, 928 patients (99.5% of the initial group) from 70 centres were randomized to the study groups. Regular assessments of symptoms were carried out every 3 months, and endoscopic examination was performed at 3,6 and 12 months, or when symptoms recurred. Gastric biopsies were taken and laboratory screening was performed before entry into the trial, and at 6 and 12 months. The end-point of the trial was endoscopically confirmed recurrence of duodenal ulcer, with or without symptoms. The remission rates, calculated using an "all patients treated" actuarial life-table analysis, are shown in Table I. Omeprazole, 20 mg once daily, maintained 87% of patients in remission at 1 year, which was significantly higher than with omeprazole, 10 mg once daily (71% in remission), and ranitidine, 150 mg nocte (63% in remission). Although the proportion of patients kept in remission with omeprazole, 10 mg once daily, was numerically greater (8% than with ranitidine at standard maintenance dose, the difference was not statistically significant (p == 0.18). Of all the ulcers that relapsed, 34% were asymptomatic. Regression analysis of prognostic factors showed higher relapse rates in patients who required a longer duration of acute treatment, irrespective of treatment, to achieve ulcer healing (p == 0.0001), in smokers (p == 0.0001), in young patients (p == 0.009) and in those with a long history of ulcer disease 0, == 0,001). Although smokers showed significantly more relapses than non-smokers, omeprazole, 20 mg once daily, was able to overcome the adverse effect of smoking on ulcer relapse. In patients over 60 years of age, omeprazole, both 10 and 20 mg once daily, was significantly more effective in preventing ulcer relapse than ranitidine, 150 mg nocte (Fig. 1). Sex, country, ulcer size and use of non-steroidal anti-inflammatory drugs did not alter the relapse rate. All treatments were well tolerated, with no clinically important changes in laboratory parameters. There was an expected, but slight, increase in serum gastrin levels, mostly within normal limits. A slight increase in grade of gastritis was observed in all treatment groups, but no evidence of dysplastic or neoplastic lesions was observed in any biopsy specimen at any time during the study. In summary, maintenance therapy with omeprazole, 20 mg once daily, in this study provided significantly higher remission rates in patients with duodenal ulcer than did ranitidine, 150 mg nocte (p == 0.000l), while omeprazole, 10 mg once daily, was found to provide numerically higher remission rates than the Hz-receptor antagonist. Furthermore, maintenance therapy with all treatments was well tolerated. From the four studies reported, it can be concluded that omeprazole, 10 mg once daily, is at least as effective as a standard dose of an H2-receptor antagonist in the maintenance treatment of duodenal ulcer, whereas omeprazole, 20 mg once daily, provides higher remission rates than either. Therefore, in the long-term treatment of duodenal ulcer disease, omeprazole, 10 mg once daily, is the recommended dose, with omeprazole, 20 mg once daily, having particular benefit in patients with severe forms of the disease, in those at risk of complications, and in patients relapsing on Hz-receptor antagonist regimens or omeprazole, 10 mg once daily. © 1994 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
