A review of medical therapy for proton pump inhibitor nonresponsive gastroesophageal reflux disease.

Up to 40% of patients report persistent gastroesophageal reflux disease (GERD) symptoms despite proton pump inhibitor (PPI) therapy. This review outlines the evidence for medical therapy for PPI nonresponsive GERD. A literature search for GERD therapies from 2005 to 2015 in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews identified 2928 unique citations. Of those, 40 unique articles specific to the impact of PPI metabolizer genotype on PPI response and the use adjunctive medical therapies were identified. Thirteen articles reported impacts on CYP genotypes on PPI metabolism demonstrating lower endoscopic healing rates in extensive metabolizers; however, outcomes across genotypes were more uniform with more CYP independent PPIs rabeprazole and esomeprazole. Twenty-seven publications on 11 adjunctive medications showed mixed results for adjunctive therapies including nocturnal histamine-2 receptor antagonists, promotility agents, transient lower esophageal sphincter relaxation inhibitors, and mucosal protective agents. Utilizing PPI metabolizer genotype or switching to a CYP2C19 independent PPI is a simple and conservative measure that may be useful in the setting of incomplete acid suppression. The use of adjunctive medications can be considered particularly when the physiologic mechanism for PPI nonresponse is suspected. Future studies using adjunctive medications with improved study design and patient enrollment are needed to better delineate medical management options before proceeding to antireflux interventions.

Review of antireflux procedures for proton pump inhibitor nonresponsive gastroesophageal reflux disease.

Up to 40% of patients with gastroesophageal reflux disease (GERD) report persistent symptoms despite proton pump inhibitor (PPI) therapy. This review outlines the evidence for surgical and endoscopic therapies for the treatment of PPI nonresponsive GERD. A literature search for GERD therapies from 2005 to 2015 in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews identified 2928 unique citations. Of those, 45 unique articles specific to surgical and endoscopic therapies for PPI nonresponsive GERD were reviewed. Laparoscopic fundoplication (n = 19) provides symptomatic and physiologic relief out to 10 years, though efficacy wanes with time. Magnetic sphincter augmentation (n = 6) and transoral incisionless fundoplication (n = 9) improve symptoms in PPI nonresponders and may offer fewer side effects than fundoplication, though long-term follow-up is lacking. Radiofrequency energy delivery (n = 8) has insufficient evidence for routine use in treating PPI nonresponsive GERD. Electrical stimulator implantation (n = 1) and endoscopic mucosal surgery (n = 2) are newer therapies under evaluation for the treatment of GERD. Laparoscopic fundoplication remains the most proven therapeutic approach. Newer antireflux procedures such as magnetic sphincter augmentation and transoral incisionless fundoplication offer alternatives with varying degrees of success, durability, and side effect profiles that may better suit individual patients. Larger head-to-head comparison trials are needed to better characterize the difference in symptom response and side effect profiles.