Mepolizumab for treatment of adolescents and adults with eosinophilic oesophagitis: a multicentre, randomised, double-blind, placebo-controlled clinical trial

Objective We aimed to determine whether mepolizumab, an anti-IL- 5 antibody, was more effective than placebo for improving dysphagia symptoms and decreasing oesophageal eosinophil counts in eosinophilic oesophagitis (EoE). Methods We conducted a multicentre, randomised, double-blind, placebo-controlled, trial. In the first part, patients aged 16-75 with EoE and dysphagia symptoms (per EoE Symptom Activity Index (EEsAI)) were randomised 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 randomised 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 randomised, 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 eos/hpf 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 endpoint 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.

Automated summary

This study aimed to determine the efficacy of mepolizumab in improving dysphagia symptoms and reducing esophageal eosinophil counts in EoE. The results showed that mepolizumab significantly decreased symptoms and eosinophil counts within 3 months, but longer treatment did not yield additional improvement.