Mepolizumab, a Humanized Monoclonal Antibody to IL-5, for Severe Eosinophilic Esophagitis in Adults: A Randomized, Placebo-Controlled Double-Blind Trial

Abstract

This pilot study evaluated the tolerability and efficacy of Mepolizumab (Mepo) in adults with severe Eosinophilic Esophagitis (EE) unresponsive to or dependent on corticosteroids. Eleven adults with active EE (>20 eos/hpf and dysphagia) were randomized to Mepo 750 mg (5, mean age 32 yr) or placebo (Pbo) (6, mean age 34 yr) by intravenous infusion at days 0 and 7. Those not in complete remission at week (Wk) 4 (<5 eos/hpf) received 2 further doses 4 weeks apart, of 1500 mg Mepo or Pbo. From the run-in period (weeks 0 to 4) and throughout the study, subjects received no other anti-eosinophil therapy. Pre- and post-treatment disease activity was assessed clinically, endoscopically, histologically and via biomarkers of inflammation. No clinically relevant adverse events occurred. A convincing decrease in mean blood eosinophils occurred with Mepo, but not with Pbo. In the esophageal tissue a similar major reduction in mean eosinophil count was observed - 82/hpf at screen to 27 at Wk 4 (-67%) in the Mepo group and from 61 to 45 (-25%) in the Pbo group. The treatment-related changes in eosinophil numbers were associated with much improvement of the swallowing difficulties in 2 subjects at 2 months post last infusion of Mepo, whereas only 1 Pbo-treated subject reported improvement. Treatment of adults with severe EE with Mepo is well tolerated. The blockade of IL-5 resulted in a highly significant decrease of eosinophil numbers in blood and esophageal tissues. These decreases were accompanied by clinical improvement in a subgroup of subjects.