Esophagus to Small Intestine
Gut. 2023;72(10):1828–37
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.