Are there unmet needs in acid suppression?

The development of proton-pump inhibitors (PPIs) caused impressive improvements in the control of gastric acid secretion. The clinically related consequences are most clearly expressed in the therapy of gastroesophageal reflux disease (GERD). Despite these glamorous outcomes, there still are unmet clinical needs. Ideally, full 24-h control of gastric acid secretion should be available to fine tune acid suppressant therapy to the individual clinical needs. Full control of acid secretion with oral PPI therapy in the presence of a healthy non-Helicobacter pylori-infected gastric mucosa is difficult, if not impossible, at present. However, there are circumstances in which full control is desirable if not essential (intensive care, esophageal columnar metaplasia, etc.). In particular, the so-called nocturnal acid breakthrough is difficult to control, particularly in patients with esophageal columnar metaplasia. But even for ordinary GERD, full symptom control and patient satisfaction is often lacking, necessating additional over-the-counter medication for control of remaining symptoms. A recent Gallup interview of 1000 symptomatic GERD patients stressed the frequency of nocturnal symptoms, insufficiently controlled with standard PPI therapy. Current PPIs are also suboptimal for 'on-demand' therapy in Non-Erosive Reflux Disease (NERD)/GERD. Moreover, rebound acid secretion after abrupt stopping of PPI therapy may favour early symptomatic relapse, necessating step-down therapy to prevent prolongation of the need of acid suppression.