Daily Esomeprazole and Erosive Esophagitis
Daily Esomeprazole and Erosive Esophagitis
Abstract & Commentary
By Malcolm Robinson MD, FACP, FACG, Emeritus Clinical Professor of Medicine, University of Oklahoma College of Medicine, Oklahoma City. Dr. Robinson serves as a consultant for TAP, Pfizer, Janssen, Eisai, J&J-Merck, and Procter & Gamble, is on the speaker’s bureau of Janssen, Eli Lilly, Solvay, TAP, and Aventis, and does research for Forest Labs, Wyeth-Ayerst, AstraZeneca, and Centocor.
Synopsis: Although this study concluded that daily therapy with esomeprazole was superior to on-demand therapy, these results remain open to question.
Source: Sjostedt S, et al. Daily treatment with esomeprazole is superior to that taken on-demand for maintenance of healed erosive oesophagitis. Aliment Pharmacol Ther. 2005; 22:183-191.
On-demand proton pump inhibitor (PPI) therapy has been shown to work well in many patients with nonerosive esophagitis, but there have been fewer studies with such intermittent treatment of erosive esophagitis (EE). Earlier trials with omeprazole and lansoprazole used on-demand in EE had not proved to be successful. Esomeprazole has been touted as more effective than earlier PPIs, and the present study was designed to compare efficacy of daily esomeprazole 20 mg with esomeprazole 20 mg taken on-demand for symptoms (but never more than one/day). All patients had Los Angeles grades A-D erosive esophagitis at original baseline with 4 or more episodes of heartburn in the week prior to study entry. All patients were treated to complete healing with esomeprazole 40 mg once daily for 4 to 8 weeks. Not only were patients required to be healed prior to randomization to maintenance therapy, they also had to be almost totally symptom-free (ie, no more than one episode of mild heartburn in the past 7 days on therapy).
Maintenance therapy with daily or on-demand esomeprazole 20 mg continued for 6 months. Patients had repeat endoscopies at 3 and 6 months and for persistent recurrent symptoms. A total of 477 patients were randomized to maintenance therapy: 243 to once daily therapy and 234 to on-demand treatment. Thirty-nine of the 'daily’ therapy patients discontinued the study, 12 for relapse and 8 for adverse events. Sixty-eight 'on demand’ patients dropped out of the study, 49 with relapse and 3 with adverse events. Also, 5.3% of patients were found to have Barrett’s esophagus at their very first baseline endoscopy, and an additional 4.9% had Barrett’s mucosa diagnosed at a subsequent endoscopy. At 6 months, 81% of patients on daily esomeprazole 20 mg had cumulatively attained endoscopic remission; of the on-demand group, 58% had attained endoscopic remission. Worse baseline esophagitis was associated with more relapses. Symptomatic relapse percentages were equally common in both groups (5% for daily vs 5.7% for on-demand therapy). Satisfaction with treatment also was comparable (96% daily therapy vs 99% on-demand esomeprazole). Despite this comparability of patient-expressed satisfaction, Sjostedt et al commented that heartburn seemed more bothersome in the on-demand group, based on a post hoc analysis of days and severity of heartburn. Adverse events were also similar between groups with the exception of more diarrhea and gastroenteritis with daily therapy.
Commentary
As Sjostedt et al comment in their discussion, overall mortality from GERD is extremely low (approximately 1 death per 100,000 patients). Thus, the primary objective of GERD therapy is the relief of symptoms and improvement of quality of life. Sjostedt et al ultimately state that on-demand therapy cannot be recommended in erosive esophagitis. However, there are many reasons to dispute that conclusion. First, although there were some patients in this study who relapsed in terms of their erosive esophagitis, we are not told whether these relapses were severe recurrences of high-grade esophagitis.
In this reviewer’s personal experience and in many discussions from expert colleagues, most such patients who do recur would manifest only very mild grades of esophagitis. Second, there are no data whatsoever to substantiate any long-term risk associated with such mucosal breaks, particularly in patients (like those in this trial) who remain minimally symptomatic and under surveillance. As the authors of this article know, a large number of patients who are prescribed continuous daily therapy opt to use their medication intermittently against medical advice. This may be cost-related in some instances, but it is also clearly associated with a wider problem of noncompliance in asymptomatic or minimally symptomatic patients. Although almost all gastroenterologists would currently treat known severe erosive esophagitis and strictures with continuous acid suppression, the consequences of on-demand therapy in less severe esophagitis remain open to question.
Although this study concluded that daily therapy with esomeprazole was superior to on-demand therapy, these results remain open to question.Subscribe Now for Access
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