Efficacy and safety of mepolizumab in hypereosinophilic syndrome: A phase III, randomized, placebo-controlled trial.

Abstract

BACKGROUND:

Anti-IL-5 therapy is a potential treatment for patients with hypereosinophilic syndrome (HES), although its clinical efficacy is unclear.

OBJECTIVE:

We sought to investigate the clinical efficacy and safety of mepolizumab versus placebo in patients with HES.

METHODS:

This randomized, multicenter, double-blind, placebo-controlled, phase III trial was conducted across 39 centers in 13 countries. Eligible patients had FIP1L1-PDGFRA-negative HES, experienced 2 or more flares (worsening of HES-related symptoms or blood eosinophil count requiring therapeutic escalation) in the previous 12 months, and had a screening blood eosinophil count greater than or equal to 1000 cells/μL. Patients were randomized (1:1) to subcutaneous mepolizumab (300 mg) or placebo every 4 weeks for 32 weeks, plus existing HES therapy. The primary outcome was the proportion of patients with 1 or more flares (worsening of HES-related symptoms necessitating therapy escalation or ≥2 courses of blinded rescue oral corticosteroids) during the study; in addition, patients who withdrew early from the study were counted as having a flare. Safety end points were also assessed.

RESULTS:

The proportion of patients experiencing 1 or more flares/withdrawing from the study was 50% lower with mepolizumab versus placebo (15 of 54 [28%] vs 30 of 54 [56%]; P = .002). Logistic regression analysis was consistent with the primary analysis (odds ratio, 0.28; 95% CI, 0.12-0.64; P = .003). Similar proportions of patients in the mepolizumab and placebo groups experienced on-treatment adverse events (48 of 54 [89%] vs 47 of 54 [87%]).

CONCLUSIONS:

Compared with placebo, mepolizumab significantly reduced the occurrence of flares in patients with HES, with no new safety signals identified.

• Authors: Florence Roufosse, Jean-Emmanuel Kahn, Marc E Rothenberg, Andrew J Wardlaw, Amy D Klion, Suyong Yun Kirby, Martyn J Gilson, Jane H Bentley, Eric S Bradford, Steven W Yancey, Jonathan Steinfeld, Gerald J Gleich, HES Mepolizumab study group
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 146 Issue 6 Pg. 1397-1405 (12 2020) ISSN: 1097-6825 [Electronic] United States
• PMID: 32956756 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• mepolizumab

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects)
• Child
• Double-Blind Method
• Eosinophils (metabolism)
• Humans
• Hypereosinophilic Syndrome (blood, drug therapy)
• Leukocyte Count
• Middle Aged