Evolving drugs in gastroesophageal reflux disease: pharmacologic treatment beyond proton pump inhibitors

Despite the clinical success of proton pump inhibitors to treat gastroesophageal reflux disease (GERD), for the majority of patients in both gastroenterology and primary care clinics there is still a substantial group of patients (up to 40% in some studies) who do not completely respond symptomatically to a standard dose of proton pump inhibitors (PPIs). Specific explanations for these PPI noncomplete responders included transient lower esophageal sphincter relaxations (TLESRs), sensitivity to weakly acidic and/or alkaline reflux, large volume of reflux and esophageal hypersensitivity. There is a clear need for GERD therapies beyond the PPIs.

These drug classes include the GABA(B) receptor agonists (including lesogaberan and arbaclofen placarbil), mGluR5 receptor antagonists, P-CABs, cholecystokinin(2) antagonists and add-on therapies to PPIs including mosapride and rikkunshito.

Both physicians and patients are eagerly awaiting the development and FDA approval of a new class of anti-GERD medications targeting distinct mechanisms. This article provides information on pharmacologic strategies, clinical trials and side-effect profiles on several of the most promising and heavily researched compounds being developed today for the treatment of GERD symptoms and inflammation. Hopefully, this important research will help a large group of PPI noncomplete responding patients receive symptomatic relief and reduce esophageal inflammation through a unique pharmacologic mechanism in the near future.

The treatment of GERD has greatly improved with the PPI class of therapy. Despite excellent success, there is a sizeable population of patients who do not have adequate response to therapies directed only at acid suppression. Emerging new pharmacologic treatment options show promise in further advancing the treatment success of GERD.