Refractory Gastroesophageal Reflux Disease

The IWGCO has undertaken the lead on the development of a Clinical Practice Guideline surrounding the diagnosis and management of refractory gastroesophageal reflux disease (rGERD).

Acid suppression therapy is effective for many patients but an estimated 10%-40% of patients with GERD have either no response or an incomplete response to a standard course of once-daily proton pump inhibitor (PPI) treatment. A survey from 2010 by the American Gastroenterological Association involving >1000 responses from patients receiving PPI therapy for GERD symptoms found that 38% reported residual symptoms, and that more than half of those with residual symptoms took additional medication to control symptoms, most commonly over-the-counter antacids (47%). Residual symptoms, despite therapy, can be attributed to one or more underlying causes including:

  1. Incomplete prevention of acid reflux into the esophagus, due to incorrect medication dose timing, medication noncompliance, residual pathologic acid secretion, rapid PPI metabolism, a hypersecretory state, a significant anatomic abnormality like a large hiatal hernia, excess reflux during transient lower esophageal sphincter relaxations (tLESRs), or defective esophageal mucosal barrier function;
  2. Reflux of normal amounts of weakly acidic or alkaline contents into a hypersensitive esophagus;
  3. Reflux of non-acid material from either the stomach or the duodenum (e.g., bile), known as duodeno-gastroesophageal reflux (DGER); DGER of bile is present in approximately 2/3rd of those patients with persistent GERD symptoms.

There is a lack of consensus on the definition of refractory GERD (rGERD) or per se a PPI non-responder. In particular, there is no agreed definition for the dose and duration of PPI treatment required to establish a diagnosis of rGERD, criteria varying from single to double dose PPIs, given for periods of 8-12 weeks.  The IWGCO recently performed an online international survey which identified a number of challenges for clinicians, especially non-GI physicians, treating patients with refractory reflux-like symptoms of GERD on a daily basis (Armstrong et al, 2022, Neurogastroenterol & Motil.). The IWGCO has also performed a population-based survey of patients with persistent reflux-like symptoms (Armstrong et al, 2023, Foregut.). where it was found that approximately 30% of survey respondents with persistent reflux symptoms had not received a formal diagnosis of GERD or rGERD.  Few respondents were satisfied with PPI therapy, as persistent symptoms and concerns relating to long-term use were prevalent.  Inadequate response to PPI therapy and opportunities for dose optimization may be under-recognized in clinical practice.

Although rGERD is a common and costly medical problem, there is, currently, no agreement with respect to the diagnostic criteria, the underlying mechanisms and the most appropriate diagnostic and therapeutic strategies. A standardized and validated, evidence-based consensus is needed if we are to make progress in the field of persistent GERD, improve patient care and provide an evidence-based approach to diagnosis and treatment.

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