title: Evolving pharmacological approaches in gastroesophageal reflux disease.
abstract: BACKGROUND
  Proton pump inhibitors (PPIs) have considerably improved quality of life in patients with gastroesophageal reflux disease (GERD). However, many patients remain symptomatic despite standard PPI therapy.
  
  
  METHODS
  This review focuses on evolving therapeutic strategies related to the pathophysiological processes of GERD and insufficient response to PPIs. Several clinical trials evaluated new PPI formulations and newer types of acid-suppressive drugs. These studies have evaluated traditional end points in GERD, but have not shown clinical superiority to current PPIs. Novel therapeutic strategies targeting underlying mechanisms of GERD, such as transient lower esophageal sphincter relaxations (TLESRs) and esophageal hypersensitivity, are being developed for add-on therapy to PPIs. Prokinetic drugs may also have some potential in the add-on treatment of GERD with insufficient response to PPIs. Add-on studies are hampered by insufficient information on optimal patient selection and lack of established end points.
  
  
  CONCLUSIONS
  Newer drugs for symptomatic control in GERD have largely focused on improved acid suppression, without evidence of clinical superiority. Drugs targeting esophageal motility and sensitivity to be used as add-onc therapy in PPI insufficient responders have not reached Phase III trials to date, due to difficulties with patient selection, tolerability and end points.
authors: University of Leuven, Translational Research Center for Gastrointestinal Disorders, Herestraat 49, B-3000, Leuven, Belgium.
authors: Ege
authors: E
authors: Altan
authors: Kathleen
authors: K
authors: Blondeau
authors: Ans
authors: A
authors: Pauwels
authors: Ricard
authors: R
authors: Farré
authors: Jan
authors: J
authors: Tack
mesh_terms: D000863:Antacids / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015154:Esophageal Motility Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D049630:Esophageal Sphincter, Lower / Q000187:drug effects / Q000503:physiopathology; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005769:Gastrointestinal Motility / Q000187:drug effects; D006801:Humans; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000863:Antacids; D054328:Proton Pump Inhibitors