Review article: Is stringent control of gastric pH useful and practical in GERD?

As the relative efficacy of therapeutic agents in the treatment of gastro-oesophageal reflux disease is related to how consistently and completely gastric acid secretion is suppressed, intragastric pH monitoring is a useful tool in stratifying therapies. If there is no acid in the stomach, there can be none to reflux into the oesophagus. Comparative crossover studies have shown consistently that once-daily esomeprazole (40 mg) provides more effective and longer lasting intragastric acid control than any other proton pump inhibitor currently available in healthy subjects and patients with gastrooesophageal reflux disease. However, esomeprazole maintained intragastric pH > 4 for ± 16 h in only about 55% of individuals tested. Thus, if more complete acid suppression is desirable, twice-daily proton pump inhibitor therapy may be advantageous. One such scenario is in patients with Barrett's metaplasia. Data from the ProGERD study suggest that, for each Los Angeles grade of oesophagitis, the healing rate for patients with Barrett's metaplasia is 10-30% less than that for non-Barrett's patients, being as low as 53% in patients with Los Angeles grade D oesophagitis. Also relevant to the Barrett's metaplasia population are studies on the oesophageal mucosa, which show that effective acid suppression favours differentiation and decreases epithelial cell proliferation. Both considerations argue for more intensive gastric acid inhibition than can be achieved with once-daily therapy, leading to experimentation with twice-daily proton pump inhibitor regimens. A randomized, double-blind, three-way crossover study compared esomeprazole 40 mg once daily with esomeprazole 20 mg and 40 mg twice daily and found that both twice-daily regimens were superior, maintaining intragastric pH > 4 for 73% [95% confidence interval (CI), 67-79%] and 80% (95% CI, 75-86%) of the day, respectively, compared with 59% (95% CI, 54-65%) of the day with esomeprazole 40 mg once daily, arguing that a twice-daily regimen may be the preferred strategy for patients with Barrett's metaplasia.