Review article: Diagnosis and management of laryngopharyngeal reflux.

BACKGROUND: Laryngopharyngeal reflux has classically referred to gastroesophageal reflux leading to chronic laryngeal symptoms such as throat clearing, dysphonia, cough, globus sensation, sore throat or mucus in the throat. Current lack of clear diagnostic criteria significantly impairs practitioners' ability to identify and manage laryngopharyngeal reflux. AIMS: To discuss current evidence-based diagnostic and management strategies in patients with laryngopharyngeal reflux. METHODS: We selected studies primarily based on current guidelines for gastroesophageal reflux disease and laryngopharyngeal reflux, and through PubMed searches. RESULTS: We assess the current diagnostic modalities that can be used to determine if laryngopharyngeal reflux is the cause of a patient's laryngeal symptoms, as well as review some of the common treatments that have been used for these patients. In addition, we note that the lack of a clear diagnostic gold-standard, as well as specific diagnostic criteria, significantly limit clinicians' ability to determine adequate therapies for these patients. Finally, we identify areas of future research that are needed to better manage these patients. CONCLUSIONS: Patients with chronic laryngeal symptoms are complex due to the heterogenous nature of symptom pathology, inconsistent definitions and variable response to therapies. Further outcomes data are critically needed to help elucidate ideal diagnostic workup and therapeutic management for these challenging patients.

Randomised clinical trial: 3-year interim analysis results of the VISION trial to evaluate the long-term safety of vonoprazan as maintenance treatment in patients with erosive oesophagitis.

BACKGROUND: VISION is a randomised, phase 4, open-label, parallel-group, multicentre study conducted in 33 centres in Japan. The aim of this study was to assess the long-term safety of vonoprazan for maintenance treatment of healed erosive oesophagitis versus lansoprazole. METHODS: Patients with endoscopically diagnosed erosive oesophagitis were randomised 2:1 to once-daily vonoprazan 20 mg or lansoprazole 30 mg, for a 4- to 8-week healing phase. Patients with endoscopically confirmed healing entered a 260-week maintenance phase with a once-daily starting dose of vonoprazan 10 mg or lansoprazole 15 mg. Primary endpoint was change in gastric mucosal histopathology. RESULTS: Of 208 patients (vonoprazan, n = 139; lansoprazole, n = 69) entering the healing phase, 202 entered the maintenance phase (vonoprazan, n = 135; lansoprazole, n = 67). At 3 years, 109 vonoprazan-treated and 58 lansoprazole-treated patients remained on treatment. Histopathological evaluation of gastric mucosa showed that hyperplasia of parietal, foveolar and G cells was more common with vonoprazan than lansoprazole at week 156 of the maintenance phase. There was no marked increase in the occurrence of parietal, foveolar and G cell hyperplasia among patients in the vonoprazan group from week 48 to week 156. Histopathological evaluation of the gastric mucosa also showed no neoplastic changes in either group. No new safety issues were identified. CONCLUSIONS: In this interim analysis of VISION, no new safety concerns were identified in Japanese patients with healed erosive oesophagitis receiving vonoprazan or lansoprazole as maintenance treatment for 3 years. (CT.gov identifier: NCT02679508; JapicCTI-163153; Japan Registry of Clinical Trials: jRCTs031180040).

Randomized clinical trial: A double-blind, proof-of-concept, phase 2 study evaluating the efficacy and safety of vonoprazan 20 or 40 mg versus esomeprazole 40 mg in patients with symptomatic gastro-esophageal reflux disease and partial response to a healing dose of a proton-pump inhibitor.

BACKGROUND: Proton-pump inhibitors (PPIs) are cornerstone treatments for gastro-esophageal reflux disease (GERD); however, evidence suggests that most patients exhibit partial response to PPIs, suggesting the need for novel therapies that can provide an improved and sustained increase in gastric pH. AIMS: This study aimed to determine the effect of vonoprazan, a novel, orally active small-molecule potassium-competitive acid blocker, versus esomeprazole, a PPI, in preventing heartburn symptoms over a 4-week treatment period in patients with GERD and a partial response to esomeprazole treatment. METHODS: This randomized, double-blind, proof-of-concept, phase 2 clinical trial was conducted between 2016 and 2018 at 39 sites across Europe and designed to evaluate the efficacy and safety of vonoprazan 20 mg once daily (q.d.) and 40 mg q.d. versus esomeprazole 40 mg q.d. after 1:1:1 randomization of symptomatic patients with GERD and a partial response to a healing dose of esomeprazole. RESULTS: Overall, 256 eligible patients (female, 59.4%; mean age, 52.6 years) received vonoprazan 20 mg (n = 85), vonoprazan 40 mg (n = 85), or esomeprazole 40 mg (n = 86); mean (SD) percentages of heartburn-free 24-h periods during double-blind treatment were 36.7% (33.4%), 36.5% (35.6%), and 38.4% (34.8%), respectively, with no intergroup statistical significance. Vonoprazan exposure increased proportionally from the 20-mg to 40-mg dose (mean Cmax : 23.3 ng/ml to 47.1 ng/ml, respectively). Most treatment-emergent adverse events were mild, with no deaths reported. CONCLUSIONS: No statistically significant difference in efficacy and safety was observed among treatment groups, and vonoprazan was well tolerated. The trial is registered with the National Board of Health (EudraCT: 2015-001154-14) database.