Efficacy and Cost Effectiveness of Lansoprazole Versus Omeprazole in Maintenance Treatment of Symptomatic Gastroesophageal Reflux Disease

Objective: To determine the dosing equivalents and cost effectiveness of lansoprazole versus omeprazole in maintenance therapy of gastroesophageal reflux disease (GERD). Study Design: Single-blind, randomized, crossover study. Patients and Methods: After completing a 1-week washout period, 27 outpatients (mean age, 66 years) with documented GERD were randomly assigned to receive omeprazole 20 mg or lansoprazole 15 mg daily for 2 weeks. The dosages were then increased to omeprazole 40 mg or lansoprazole 30 mg daily for an additional 2 weeks. All patients completed a second 1-week washout period before crossing over to the alternate agent. Patients recorded GERDrelated symptoms (heartburn, chest pain, and regurgitation) daily in a diary. The total symptom score (the sum of the 3 individual symptom scores) were compared for all treatments. Cost effectiveness was evaluated by determining the cost per percent reduction in the total symptom score. Results: All treatment groups had significant reductions from baseline in the total symptom score From the University of the Sciences in Philadelphia, Philadelphia College of Pharmacy, Department of Pharmacy Practice and Pharmacy Administration, Philadelphia, PA (E.V. and E.B.); and Veterans Affairs San Diego Healthcare System, Pharmacy Service, San Diego, CA (A.M., K.L., O.E., and P.H.). This study was funded by TAP Pharmaceuticals, Inc., Deerfield, IL. Address correspondence to: Eva Vivian, PharmD, Assistant Professor of Clinical Pharmacy, Department of Pharmacy Practice and Pharmacy Administration, University of the Sciences in Philadelphia, Philadelphia College of Pharmacy, 600 South FortyMany patients with gastroesophageal reflux disease (GERD) require medication for relief of symptoms. Agents such as antacids, alginic acid, and sucralfate provide symptomatic relief in patients with mild to moderate symptoms. Although cisapride and the H2-antagonists (ranitidine, cimetidine, nizatidine, and famotidine) are effective for relieving heartburn pain and healing mild to moderate esophagitis, the proton pump inhibitors (omeprazole and lansoprazole) are currently the most effective agents for relieving GERD symptoms and healing esophageal lesions.1-3 Proton pump inhibitors are often prescribed for patients who do not respond adequately to H2antagonists.4 Omeprazole and lansoprazole decrease gastric acid secretion over a 24-hour period by binding irreversibly to the H+/K+ ATPase pump at the surface of (P < 0.01). No significant difference was seen between lansoprazole 15-mg and omeprazole 20-mg groups or the the lansoprazole 30-mg and omeprazole 40-mg groups. Lansoprazole 15 mg was found to be as effective as omeprazole 40 mg and omeprazole 20 mg was as effective as lansoprazole 30 mg. The average cost per percent reduction in total symptom score was $0.03 for the lansoprazole 15-mg, lansoprazole 30-mg, and omeprazole 20-mg doses and $0.05 for the omeprazole 40-mg dose. Conclusion: Lansoprazole is as effective as omeprazole in providing symptomatic relief of GERD. Based on acquisition cost, lansoprazole is more cost effective than omeprazole. (Am J Manag Care 1999;5:881-886) the parietal cell. The acid-suppressive effects of lansoprazole 30-mg, omeprazole 20-mg, and famotidine 20-mg were measured in 10 healthy volunteers with no history of gastrointestinal problems using 24hour intragastric pH monitoring. Omeprazole and lansoprazole were more effective at inhibiting daytime and nocturnal acid secretion than was famotidine, an H2-antagonist. Because patients with GERD have a high rate of relapse within 1 year after discontinuing drug therapy, maintenance treatment is highly recommended. Five therapies (ranitidine, cisapride, omeprazole, ranitidine plus cisapride, and omeprazole plus cisapride) were compared in the maintenance treatment of reflux esophagitis. Omeprazole alone or in combination with cisapride was more effective than ranitidine, cisapride, or the combination of ranitidine and cisapride.6 Dosing equivalence has been evaluated in a number of studies. In one study,7 lansoprazole 30-mg and omeprazole 20-mg were more effective than lansoprazole 15-mg in healing esophageal lesions in patients with erosive reflux esophagitis. In addition, lansoprazole 30-mg provided greater symptomatic relief than did lansoprazole 15-mg or omeprazole 20-mg during the early treatment period. In another study,4 lansoprazole 30-mg provided greater symptomatic relief in reflux esophagitis than did omeprazole 20-mg during the first week of the study. Before 1997, omeprazole was the only proton-pump inhibitor on the formulary at the Veterans Affairs San Diego Healthcare System. Lansoprazole replaced omeprazole on the VAMC national formulary in January 1997. At that time, no published studies had examined the relative dosing equivalents and cost effectiveness of lansoprazole versus omeprazole in the maintenance treatment of GERD. Consequently, our goal in conducting this study was to compare the dosing equivalents and cost effectiveness of low and high doses of lansoprazole and omeprazole. . . . PATIENTS AND METHODS . . . Patients were eligible for the study if they had a confirmed diagnosis of chronic GERD based on clinical presentation or results of invasive procedures such as endoscopy, were currently being seen in a gastrointestinal or general medicine clinic, and were currently receiving omeprazole for maintenance treatment of GERD. Patients taking phenytoin, warfarin, or diazepam were excluded because omeprazole inhibits the metabolism of these agents. Patients receiving theophylline were excluded as well because concomitant use of lansoprazole can increase the clearance of theophylline. Also excluded were patients prescribed cisapride concomitantly with omeprazole to control symptoms of GERD and those with a documented diagnosis of esophageal stricture, primary esophageal motility disorder, or a confirmed malignancy. The University of California at San Diego Investigation Review Board and the Veterans Affairs San Diego Investigation Review Board approved the research protocol. Each patient provided written consent before enrollment. Medication was administered using the randomized, crossover design shown in Figure 1. Because of limited resources, we used a single-blind design. Patients were randomized into 2 groups using a random number chart. All patients completed a 1-week washout period before initial treatment to determine their baseline GERD symptoms. During the washout period, patients were allowed to use Extra Strength Maalox® (Ciba Self-Medication, Inc., Woodbridge, NJ) as needed for symptomatic relief. Group A received omeprazole 20-mg once daily for 2 weeks then omeprazole 40-mg once daily for an additional 2 weeks. Group B received lansoprazole 15-mg once daily for 2 weeks then lansoprazole 30mg once daily for an additional 2 weeks. After this 4-week treatment period, patients again completed a 1-week washout period before switching to the alternate study drug. Extra Strength Maalox® was permitted during this washout as well. . . . HEALTH ECONOMICS . . . 882 THE AMERICAN JOURNAL OF MANAGED CARE JULY 1999 Figure 1. Study Design Week 1 Weeks 2 and 3 Weeks 4 and 5 Week 6 Weeks 7 and 8 Weeks 9 and 10 Group A Washout Omeprazole 20 mg Omeprazole 40 mg Washout Lansoprazole 15 mg Lansoprazole 30 mg Group B Washout Lansoprazole 15 mg Lansoprazole 30 mg Washout Omeprazole 20 mg Omeprazole 40 mg The omeprazole 20-mg capsules (Astra Merck, Wayne, PA) and lansoprazole 15-mg capsules (TAP Pharmaceuticals Inc., Deerfield, IL) were repackaged in a blue gelatin capsule shell to prevent patients from knowing which medication they were receiving. We used the Vigneri symptom assessment diary to assess GERD symptoms.6 Patients were given the diary and asked to record daily the severity and frequency of their GERD symptoms (heartburn, chest pain, and regurgitation). We called each patient weekly to gather data on changes in symptoms. Because we did not include a pill count as part of the study, patients were asked about compliance during the call. Patients also were monitored (via diary entries and phone follow-up) for adverse effects, including diarrhea, abdominal pain, nausea, vomiting, constipation, flatulence, and rash. The severity of symptoms was assessed as follows: grade 0 = no symptoms, grade 1= mild symptoms, grade 2 = moderate symptoms with mild interference with lifestyle and sleep, and grade 3 = severe symptoms with interference with lifestyle and sleep. The frequency of symptoms was assessed as follows: grade 0 = no symptoms, grade 1 = less than 2 days a week, grade 2 = 2 to 4 days a week, and grade 3 = more than 4 days a week. We calculated a score for each symptom and a total symptom score. To calculate the individual symptom score, we multiplied the severity grade by the frequency grade (range, 0-9). To calculate the total symptom score, we summed each of the 3 individual symptom scores (range, 0-27). Although no dietary restrictions were prescribed for patients enrolled in the study, they were educated about nonpharmacologic means of preventing GERD symptoms (eg, decreasing fat and caffeine intake, avoiding chocolate and peppermint, stopping tobacco use, and elevating the head of their bed).8,9 Because more than 50% of patients at our medical center take drugs that can aggravate GERD symptoms (eg, anticholinergic agents, β-blockers, and calcium channel blockers), we thought it appropriate to include patients taking such medications in our study since they served as their own control. We evaluated the cost effectiveness of lansoprazole and omeprazole by determining the cost per percent reduction in the total symptom score. Hospitalizations and time lost from work were not assessed. At the time we conducted the study, the acquisition cost per capsule for omeprazole 20 mg was $1.67 and for lansoprazole 15 mg and 30 mg cost per capsule was $1.50. Statistical Analysis Assuming that a 40% reduction in the total symptom score from baseline would be clinically significant using and α value of 0.05 and a β value of 0.20, we needed a sample size of 10 patients to detect a statistically significant difference between the 4 treatment groups (assuming a baseline total symptom score of 14 and standard deviation ± 9. If we assumed that a 25% difference between the effects of active drug or different doses would be clinically significant using an α of 0.05 and a β of 0.20, the required sample size would be 25 patients. We compared the 4 treatment groups using Friedman’s analysis of variance, a nonparametric test for related measures. Wilcoxon’s signed-rank test for paired data was used as a post-hoc test with statistical significance set at P < .001 to decrease the effect of multiple comparisons. All statistical tests were two-tailed and considered significant when P < .05. We used the SPSS statistical package for our analyses. Power analysis revealed that 459 patients would have been needed to detect a difference between the low-dose omeprazole and low-dose lansoprazole groups.