Long-term effect on symptoms and quality of life of maintenance therapy with esomeprazole 20 mg daily: a post hoc analysis of the LOTUS trial

Abstract

Objective:

To assess the long-term effect on symptoms and quality of life of esomeprazole 20 mg once daily, a recommended dose for maintenance therapy of gastroesophageal reflux disease (GERD).

Research design and methods:

This is a post hoc analysis of 5 year data from patients in the LOTUS trial (ClinicalTrials.gov identifier: NCT00251927) who were randomized to esomeprazole 20 mg once daily. All participants had chronic, symptomatic GERD responsive to treatment. Gastrointestinal symptoms were assessed by physicians and by using patient-reported outcome instruments. Investigations included gastrointestinal endoscopy (with biopsy sampling), 24 hour esophageal pH monitoring and laboratory measurements.

Results:

In total, 157 of 256 patients randomized to esomeprazole 20 mg once daily remained on this dose until the end of follow-up or study discontinuation, whereas 99 patients had their dose increased because of inadequate symptom control (of these, 29 subsequently returned to the allocated dose). On logistic regression, a long objectively defined GERD history, smoking, female sex, absence of Helicobacter pylori infection and high supine baseline acid reflux into the esophagus were associated with an increased likelihood of requiring dose escalation to esomeprazole 40 mg daily (all p < 0.05). Symptoms were fairly stable and quality of life was normal throughout follow-up in patients remaining on esomeprazole 20 mg once daily, with no more than mild symptom severity, and mean (standard deviation) percentage time with intraesophageal pH <4 was reduced from 10.7 (10.7) pre-randomization to 6.3 (10.2) at 6 months and 4.9 (7.3) at 5 years. The number of serious adverse events was low (0.079 per patient per year).

Limitations:

Post hoc analysis with no control group.

Conclusions:

Esomeprazole at a maintenance dose of 20 mg once daily offers effective long-term treatment for chronic GERD in patients initially responsive to the medication, with durable symptom control and sustained reductions in intraesophageal acid exposure.

Trial registration: ClinicalTrials.gov identifier: NCT00251927.

Keywords: :

• Enterochromaffin cells
• Gastritis
• Gastroesophageal reflux
• Helicobacter pylori
• Long-term care
• Proton pump inhibitors
• Safety

Transparency

Declaration of funding

The work was funded by AstraZeneca R&D, Mölndal, Sweden.

Declaration of financial/other relationships

L.L. and J.H. have disclosed that they were members of the steering committee for LOTUS, but have no other relevant financial relationships to disclose. J.-P.G. has disclosed that he is a consultant for AstraZeneca, MKT, Shire and Given Imaging. S.E.A. has disclosed that he was also a member of the steering committee for LOTUS, and has disclosed being a speaker for AstraZeneca, and a previous speaker for Ethicon Endosurgery. C.E. has disclosed that he has received grants for research from AstraZeneca, Fujinon, Erbe, and Hitachi. R.F. has disclosed that he has received support for travel and related expenses for attending study associated meetings and his institution received a grant from AstraZeneca for central histological analyses. P.N., S.E., and T.P. have disclosed that they are employees of AstraZeneca R&D, Mölndal, Sweden. T.L. has disclosed that he is a consultant and former employee of AstraZeneca R&D, Mölndal, Sweden.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no other relevant financial relationships to disclose.

Acknowledgments

Writing support was provided by Dr Anja Becher, from Oxford PharmaGenesis Ltd, Oxford, UK, and was funded by AstraZeneca R&D, Mölndal, Sweden.