Management of gastroesophageal reflux disease that does not respond well to proton pump inhibitors

Purpose of review Patients with gastroesophageal reflux disease (GERD) who are not responding to proton pump inhibitors (PPIs) given once daily are very common. These therapy-resistant patients have become the new face of GERD in clinical practice in the last decade and presently pose a significant therapeutic challenge to the practicing physician. We reviewed newly accumulated information about the management of PPI failure that has been published over the past 2 years. Recent findings There are diverse mechanisms that contribute to the failure of PPI treatment in GERD patients and they are not limited to residual reflux. Some of the causes of PPI failure may coincide in the same patient. Upper endoscopy appears to have limited diagnostic value. In contrast, esophageal impedance with pH testing on therapy appears to provide the most insightful information about the subsequent management of these patients. Commonly, doubling the PPI dose or switching to another PPI will be offered to patients who failed PPI once daily. Failure of such therapeutic strategies is commonly followed by assessment for residual reflux. There is growing information about the potential value of compounds that can reduce transient lower esophageal sphincter relaxations. Esophageal pain modulators are commonly offered to patients with functional heartburn, although supportive clinical studies are still missing. Summary Management of refractory GERD patients remains an important clinical challenge. Recent studies have cemented the value of impedance-pH testing in pursuing proper treatment. Presently, the most promising therapeutic development for this patient population is transient lower esophageal sphincter relaxation reducers.