Trial confirms long-term safety and efficacy of mepolizumab for HES

Published Online: October 12, 2012

Hypereosinophilic syndromes (HES) are chronic inflammatory disorders characterized by increased blood eosinophil counts associated with potentially life-threatening eosinophilic organ damage. Although a majority of patients respond initially to corticosteroids (CS), long-term maintenance therapy is generally needed. Consequently, development of drug resistance and debilitating side effects are common. Mepolizumab, a monoclonal antibody targeting the major eosinophil growth factor, interleukin-5, was recently shown to be effective and well-tolerated as a CS-sparing agent in a double-blind placebo-controlled trial in patients with HES.

In a recent original article published in The Journal of Allergy and Clinical Immunology (JACI), Roufosse et al reported the results of an open-label extension to the prior placebo-controlled study. The open-label study was designed to evaluate the long-term safety and efficacy of mepolizumab in patients with HES. Seventy-eight patients received mepolizumab for an average of 4.8 years. CS doses were adapted at the physicians’ discretion, and adverse events (AE) were recorded throughout the observation period. Eosinophil counts were closely monitored. Once a stable response to mepolizumab was documented, the optimal dosing frequency was determined by withholding mepolizumab until blood eosinophil counts began to rise and/or symptoms returned.

The authors found that the incidence of AEs per 100 subject-years was similar to that observed in the placebo-controlled trial and decreased over the duration of the open-label study. Less than one-third of the AEs were reported as possibly related to mepolizumab treatment, the large majority of which were non-specific (fatigue, nausea) and mild in intensity. Four deaths occurred during the 5 years of the study, of which only one was reported as possibly drug-related. The response rate to mepolizumab in this patient population was high, with only six patients withdrawn due to lack of efficacy. Eosinophils were well-controlled throughout the trial despite the fact that more than half of patients were durably tapered off CS. The average interval between mepolizumab infusions was more than 12 weeks. None of the patients became resistant to treatment during the trial, and there was no evidence of decreased response to mepolizumab over time. Two-thirds of the patients continued to receive mepolizumab at the end of the study.

The authors concluded that prolonged reduction of eosinophilia using mepolizumab is well-tolerated and effective as a CS-sparing strategy in patients with HES. Although mepolizumab is not currently FDA-approved, these data provide hope that novel therapies targeting eosinophils will provide long-term alternatives to CS therapy for patients with HES in the future.


The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

AAAAI - American Academy of Allergy Asthma & Immunology