Novel pharmaceutical approaches to reflux disease.

Acid suppression, with proton pump inhibitors (PPI), is the mainstay of therapy for reflux disease; despite this, symptoms and injury persist in many patients. Novel approaches have focused on (1) augmenting acid suppression with reformulated current PPIs, new PPIs or new acid pump blockers and (2) preventing reflux with reflux inhibitors. Other strategies to reduce reflux, improve gastric emptying or esophageal clearance, protect the mucosa, or reduce esophageal sensitivity are under investigation alone or in combination with PPIs; however, novel approaches face significant challenges. The safety and efficacy of current PPIs hamper demonstration of clinical superiority for new acid suppressants, and the multifactorial etiology of reflux disease means that monotherapy using a non-acid suppressant is unlikely to match PPI therapy while combination therapy will be superior only if susceptible patients can be identified reliably. Advances will come, not from a 'one size fits all' approach but rather from novel pharmaceuticals allied to novel investigations to permit targeted, personalized reflux therapy.