Summary and Introduction

Summary

Background: Proton pump inhibitors are the most potent drug treatment for gastro-oesophageal reflux disease. Premeal dosing maximizes efficacy while sub-optimal dose timing may limit efficacy.
Aim: To determine the prevalence of sub-optimal proton pump inhibitor dosing in a community-based gastro-oesophageal reflux disease population.
Materials and methods: One hundred patients on proton pump inhibitors referred for persistent gastro-oesophageal reflux disease symptoms were questioned about their proton pump inhibitor dosing habits and classified as optimal or sub-optimal dosers. Optimal dosers took proton pump inhibitors with or up to 60 min before meals. Sub-optimal dosers took proton pump inhibitors >60 min before meals, after meals, as needed, or at bedtime.
Results: Forty-six percent dosed optimally. Fifty-four percent dosed sub-optimally with 21 of 54 (39%) dosing >60 min before meals, 16 (30%) after meals, 15 (28%) at bedtime and two (4%) as needed. Only 6% of the subjects on once-daily proton pump inhibitor regimens and 33% of subjects taking proton pump inhibitors two- to three times daily dosed in a manner that maximized acid suppression (15–30 min before a meal).
Conclusions: In this study, 54% of patients dosed proton pump inhibitors sub-optimally and only 12% dosed in a manner that maximized acid suppression. As sub-optimal proton pump inhibitor dose timing can limit efficacy, patients with refractory symptoms should be asked about dose timing to avoid inappropriate and costly dose escalations.

Introduction

Gastro-oesophageal reflux disease (GERD) is a common and costly clinical syndrome. Up to one-half of all American adults experience symptoms of heartburn at least once a month^[1-2] and 4–7% have daily reflux symptoms.^[3] A questionnaire-based study conducted in Minnesota revealed that the prevalence of either heartburn or acid regurgitation in the past year was 59/100 and 20/100 for at least weekly symptoms.^[4] Dyspepsia is associated with over 2 million out-patient doctor visits annually and almost 40% of gastroenterology referrals in the US.^[5-6] It has been estimated that in the US more than $2 billion are spent per year on over-the-counter antacids and histamine-2 receptor antagonists. In addition, it is estimated that $6 billion are spent on prescription histamine-2 receptor antagonists and proton pump inhibitors (PPIs).^{[2, 3, 7]} A recent evaluation of a rural northeastern managed care organization revealed the mean annual cost of treating GERD patients over nine study years was approximately $510/year and patients with GERD incurred approximately twofold higher medical care costs compared with those without GERD.^[8]

Gastro-oesophageal reflux disease therapy options range from lifestyle modifications to pharmacologic treatment with motility agents, histamine-2 receptor antagonists and PPIs.^[9] In comparison studies, PPIs have consistently exhibited superior efficacy in the treatment of GERD symptoms and GERD-associated oesophageal erosions.^[9-13] To inhibit gastric acid secretion PPIs must accumulate in the acidic environment of actively secreting parietal cells, undergo conversion to a reactive species via an acid-catalyzed reaction, and covalently inhibit ATPase molecules recruited to the luminal parietal cell surface.^{[12, 14]} As gastric acid secretion is maximally stimulated by food ingestion, maximal PPI efficacy should be achieved when they are taken before a meal.^[12-14] The concept of premeal PPI dosing has been validated in several intragastric pH probe studies.^[14-16] The objective of this study was to examine PPI dosing practices in GERD patients with poor symptom control. Our specific aim was to assess the prevalence of sub-optimal PPI dose timing in GERD patients with poor symptom control within a community-based gastroenterology practice.