Proton Pump Inhibitor-Refractory Gastroesophageal Reflux Disease

Proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) is defined by the presence of troublesome GERD symptoms despite PPI optimization for at least 8 weeks in the setting of ongoing documented pathologic gastroesophageal reflux. It arises from a dysfunction in protective systems to prevent reflux and as propagation of physiologic reflux events. Treatment possibilities include pharmacologic options, invasive management strategies, and endoluminal therapies. Management strategy should be personalized to the patient's needs and mechanistic dysfunction. This article reviews the definition, mechanisms, and management options for PPI-refractory GERD.