Esophagus to Small Intestine

Gut. 2023;72(10):1828–37

Dellon ES, Peterson KA, Mitlyng BL, Iuga A, Bookhout CE, Cortright LM, Walker KB, Gee TS, McGee SJ, Cameron BA, Galanko JA, Woosley JT, Eluri S, Moist SE, Hirano I

Mepolizumab for treatment of adolescents and adults with eosinophilic esophagitis: A multicenter, randomized, double-blind, placebo-controlled clinical trial


Objective: The aim of this study was to determine whether mepolizumab, an anti-IL-5 antibody, was more effective than placebo for improving dysphagia symptoms and decreasing esophageal eosinophil counts in eosinophilic esophagitis (EoE).
Methods: A multicenter, randomized, double-blind, placebo-controlled trial was conducted. In the first part, patients aged 16–75 years with EoE and dysphagia symptoms (per EoE Symptom Activity Index [EEsAI]) were randomized 1:1 to 3 months of mepolizumab 300 mg monthly or placebo. Primary outcome was change in EEsAI from baseline to month 3 (M3). Secondary outcomes included histological, endoscopic and safety metrics. In part 2, patients initially randomized to mepolizumab continued 300 mg monthly for 3 additional months (mepo/mepo), placebo patients started mepolizumab 100 mg monthly (pbo/mepo), and outcomes were reassessed at month 6 (M6).
Results: Of 66 patients randomized, 64 completed M3, and 56 completed M6. At M3, EEsAI decreased 15.4 ± 18.1 with mepolizumab and 8.3 ± 18.0 with placebo (p = 0.14). Peak eosinophil counts decreased more with mepolizumab (113 ± 77 to 36 ± 43) than placebo (146 ± 94 to 160 ± 133) (p < 0.001). With mepolizumab, 42% and 34% achieved histological responses of < 15 and ≤ 6 eosinophils/high-power field compared with 3% and 3% with placebo (p < 0.001 and 0.02). The change in EoE Endoscopic Reference Score at M3 was also larger with mepolizumab. At M6, EEsAI decreased 18.3 ± 18.1 points for mepo/mepo and 18.6 ± 19.2 for pbo/mepo (p = 0.85). The most common adverse events were injection-site reactions.

Conclusions: Mepolizumab did not achieve the primary end point of improving dysphagia symptoms compared with placebo. While eosinophil counts and endoscopic severity improved with mepolizumab at 3 months, longer treatment did not yield additional improvement.

E.S. Dellon, M.D., Professor of Medicine, Center for Esophageal Diseases and Swallowing, and Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA, E-Mail: edellon@med.unc.edu

DOI: 10.1136/gutjnl-2023-330337

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