Treatment modalities for gastro-oesophageal reflux disease (GORD) mirror the pathophysiology of the disease. Since acid plays a key role in GORD-associated mucosal lesions, proton pump inhibitors (PPIs) are the dominant GORD treatment, being the most potent inhibitors of acid secretion available. However, the clinical effectiveness of PPIs varies with the specific symptoms being treated; they are more effective for heartburn than for regurgitation than for extra-oesophageal symptoms. An alternative therapeutic approach to GORD is to prevent the most fundamental cause of reflux symptoms, reflux itself, which most commonly occurs by transient lower oesophageal sphincter relaxation (TLOSR). Among potential pharmaceutical agents developed to target TLOSRs, the most advanced are GABAB (γ-aminobutyric acid) agonists, which experimentally reduce the occurrence of TLOSRs by about 40% in both animal and human studies. However, the effectiveness of GABAB agonists in clinical trials of patients with GORD with an incomplete response to PPI treatment has been modest. In part, this is probably attributable to the difficult problem of patient selection in these trials. Identifying patients by partial response to PPI treatment results in a heterogeneous population, including those with persistent weakly acidic reflux, patients with visceral hypersensitivity and those with functional heartburn, dyspepsia, or chest pain. From the clinical data available, the best treatment results and, hence, the patients most likely to benefit from reflux inhibitors, are those with persistent reflux, most commonly manifest as persistent regurgitation despite PPI treatment.
- Gastro-oesophageal reflux disease
- drug development
- proton pump inhibitors
- gastro-oesopahgeal junction
- antireflux therapy
- autonomic nervous system
- oesophageal pH monitoring
- oesophageal physiology
- oesophageal reflux
- motility disorders
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.
This is a reprint of a paper that first appeared in the Journal of Gastroenterology and Hepatology, 2012, Volume 61, pages 1501–9.
Competing interests PJK is a paid consultant for AstraZeneca, Eisai, EndoGastric Soultions, Ironwood Pharmaceuticals, Reckitt Benchiser, Torax and Xenoport. He receives grant support from the US National Institute of Health (R01 DC00646) and Reckitt Benchiser. GB serves on an advisory board and speakers bureau for Shire-Movetis. He is a paid consultant for Reckitt Benchiser and Shire-Movetis.
Provenance and peer review Commissioned; externally peer reviewed.