Lansoprazole and Esomeprazole in Symptomatic GERD

William Chey, Bidan Huang, Robert L. Jackson

Disclosures

Clin Drug Invest. 2003;23(2) 

In This Article

Abstract and Introduction

Objective: To evaluate the onset and degree of symptom relief in a population of patients with symptomatic gastro-oesophageal reflux disease (GERD) treated with lansoprazole 30mg or esomeprazole 40mg, each administered once daily.
Design: This was a phase IIIb, prospective, randomised, double-blind, active-controlled, multicentre study of patients with a history of symptomatic GERD.
Methods: Patients with symptomatic GERD based on preset criteria were randomised in a 1 : 1 ratio to lansoprazole or esomeprazole for 2 weeks. Efficacy endpoints were the percentage of patients without daytime heartburn after the first treatment day, the percentage of patients without night-time heartburn after the first treatment day, and symptom relief (measured as percentage of days and nights without heartburn) and average symptom severity after the first day, during the first 3 days (primary efficacy endpoint), during the first week and during the 2-week treatment period.
Results: 3034 patients were randomised to lansoprazole 30mg (n = 1520) or esomeprazole 40mg (n = 1514). Patients in both treatment groups reported increases from baseline in the percentages of days and nights without heartburn and decreases in the average daytime and night-time heartburn severity during the 2-week treatment period. No statistically significant differences were observed between the lansoprazole 30mg and esomeprazole 40mg treatment groups in heartburn relief parameters on day 1 or during the first 3 days, the first week or the 2-week treatment period after adjusting for differences in baseline heartburn severity. Both treatments were well tolerated. Significantly higher percentages of patients treated with esomeprazole as compared with those treated with lansoprazole reported treatment-emergent dry mouth (0.5% vs 0.1%, p = 0.021) and vomiting (0.5% vs 0.1%, p = 0.038). The most common treatment-related adverse events were diarrhoea (lansoprazole 1.4%, esomeprazole 1.8%), flatulence (lansoprazole 0.7%, esomeprazole 1.0%) and abdominal pain (lansoprazole 1.1%, esomeprazole 1.3%).
Conclusion: Lansoprazole 30mg once daily or esomeprazole 40mg once daily for 2 weeks effectively increase the percentage of days and nights patients with symptomatic GERD are without heartburn and reduce the average severity of daytime and night-time heartburn.

Among the medical therapies for gastro-oesophageal reflux disease (GERD), proton pump inhibitors (PPIs) are the most effective in terms of symptom improvement, healing of erosive oesophagitis and maintenance of remission.[1,2,3,4,5,6,7,8] Although the superiority of PPIs as a class is not in question, uncertainties remain regarding the relative efficacy of individual PPIs for the treatment of GERD. Many studies that have evaluated different medical therapies or compared individual PPIs for GERD have focused on the healing of erosive oesophagitis. Healing of oesophagitis provides a relatively objective endpoint for clinical studies, but it is not the most relevant endpoint for the clinician as the vast majority of patients with symptoms suggestive of GERD do not undergo endoscopy. Furthermore, even if one considers only those symptomatic patients who undergo endoscopy, studies suggest that <50% will have erosive oesophagitis.[9,10] Therefore, from a pragmatic standpoint, the most clinically relevant end-point in patients with suspected GERD is symptomatic improvement.

Among the currently available PPIs, study results suggest differences in the proportions of individuals who report adequate or complete symptom relief at specific predetermined time-points and in the onset of symptom relief.[11,12,13,14,15,16] This effect may in part be due to differences in the pharmacokinetic profiles of these agents. For example, the bioavailability of lansoprazole is approximately 85% following the first dose and remains so with repeat administration, whereas the bioavailability of omeprazole is approximately 40% following the initial dose and rises to approximately 65% with repeated administration. In a recent meta-analysis, lansoprazole 30mg once daily was found to be more effective than omeprazole 20mg once daily in the speed of relieving heartburn among patients with erosive oesophagitis.[11] A large double-blind, randomised study of over 3500 patients found that a significantly higher percent-age of patients treated with lansoprazole 30mg once daily did not experience heartburn after 1 day of treatment as compared with those treated with omeprazole 20mg on the first day of treatment (33% vs 25%, p < 0.0001). The difference between the two treatments persisted throughout the entire 8-week treatment period.[12]

Results of heartburn efficacy studies involving recently released PPIs such as esomeprazole have not been as conclusive. Esomeprazole, an isomer of omeprazole, also has an absolute bioavailability that increases with continuous use, from 50% to 68% with a dosage of 20 mg/day and from 64% to 89% with a dosage of 40 mg/day.[17] However, studies that compared the efficacy of lansoprazole and esomeprazole on heartburn relief, whether as a primary or secondary endpoint, have found conflicting results.[13,14,15] A recent meta-analysis published in abstract form found a numerically small, but statistically significant, difference in favour of esomeprazole 40mg over lansoprazole 30mg, omeprazole 20mg and esomeprazole 20mg in the onset of nocturnal heartburn relief after 1 week of treatment.[16] In general, factors such as study selection, patient population, study methodology and inclusion/ exclusion criteria may influence the findings of meta-analysis data, thereby limiting our ability to interpret their findings.

In order to clarify these disparate conclusions regarding the onset and efficacy of daytime and night-time heartburn relief between lansoprazole 30mg once daily and esomeprazole 40mg once daily, we designed this large-scale, randomised, multicentre, double-blind, prospective clinical study. The objectives of this trial were to evaluate the onset and degree of symptom relief in a population of patients with heartburn symptoms suggestive of GERD treated with lansoprazole 30mg or esomeprazole 40mg, each administered once daily.

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