Gastroenterology
Author:
Keywords:
Science & Technology, Life Sciences & Biomedicine, Gastroenterology & Hepatology, Phase 3 Trial, Immune Response, Esophagus, Patient-Reported Outcomes, HISTOLOGIC REMISSION, ADULT PATIENTS, CHILDREN, RECOMMENDATIONS, FLUTICASONE, VALIDATION, SUSPENSION, DYSPHAGIA, SYMPTOMS, DISEASE, Administration, Oral, Adult, Antifungal Agents, Budesonide, Candidiasis, Oral, Double-Blind Method, Eosinophilic Esophagitis, Esophagoscopy, Female, Glucocorticoids, Humans, Male, Middle Aged, Tablets, Treatment Outcome, International EOS-1 Study Group, esophagus, immune response, patient-reported outcomes, phase 3 trial, 1103 Clinical Sciences, 1109 Neurosciences, 1114 Paediatrics and Reproductive Medicine, 3202 Clinical sciences, 3210 Nutrition and dietetics
Abstract:
BACKGROUND & AIMS: Swallowed topical-acting corticosteroids are recommended as first-line therapy for eosinophilic esophagitis (EoE). Asthma medications not optimized for esophageal delivery are sometimes effective, although given off-label. We performed a randomized, placebo-controlled trial to assess the effectiveness and tolerability of a budesonide orodispersible tablet (BOT), which allows the drug to be delivered to the esophagus in adults with active EoE. METHODS: We performed a double-blind, parallel study of 88 adults with active EoE in Europe. Patients were randomly assigned to groups that received BOT (1 mg twice daily; n = 59) or placebo (n = 29) for 6 weeks. The primary end point was complete remission, based on clinical and histologic factors, including dysphagia and odynophagia severity ≤2 on a scale of 0-10 on each of the 7 days before the end of the double-blind phase and a peak eosinophil count <5 eosinophils/high power field. Patients who did not achieve complete remission at the end of the 6-week double-blind phase were offered 6 weeks of open-label treatment with BOT (1 mg twice daily). RESULTS: At 6 weeks, 58% of patients given BOT were in complete remission compared with no patients given placebo (P < .0001). The secondary end point of histologic remission was achieved by 93% of patients given BOT vs no patients given placebo (P < .0001). After 12 weeks, 85% of patients had achieved remission. Six-week and 12-week BOT administration were safe and well tolerated; 5% of patients who received BOT developed symptomatic, mild candida, which was easily treated with an oral antifungal agent. CONCLUSIONS: In a randomized trial of adults with active EoE, we found that budesonide oral tablets were significantly more effective than placebo in inducing clinical and histologic remission. Eudra-CT number 2014-001485-99; ClinicalTrials.gov ID NCT02434029.