Long-term safety of mepolizumab for the treatment of hypereosinophilic syndromes

Background Hypereosinophilic syndromes (HESs) are chronic disorders that require long-term therapy to suppress eosinophilia and clinical manifestations. Corticosteroids are usually effective, yet many patients become corticosteroid refractory or develop corticosteroid toxicity. Mepolizumab, a humani...

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Published in:Journal of allergy and clinical immunology 2013-02, Vol.131 (2), p.461-467.e5
Main Authors: Roufosse, Florence E., MD, Kahn, Jean-Emmanuel, MD, Gleich, Gerald J., MD, Schwartz, Lawrence B., MD, Singh, Anish D., MD, Rosenwasser, Lanny J., MD, Denburg, Judah A., MD, Ring, Johannes, MD, Rothenberg, Marc E., MD, PhD, Sheikh, Javed, MD, Haig, Ann E., BSN, Mallett, Stephen A., MSc, Templeton, Deborah N., MSN, Ortega, Hector G., MD, ScD, Klion, Amy D., MD
Format: Article
Language:English
Subjects:
Adolescent
Adrenal Cortex Hormones - adverse effects
Adrenal Cortex Hormones - therapeutic use
Adult
Aged
Allergy and Immunology
Antibodies
Antibodies, Monoclonal, Humanized - adverse effects
Antibodies, Monoclonal, Humanized - immunology
Antibodies, Monoclonal, Humanized - therapeutic use
Biological and medical sciences
Blood
Cancer
Clinical trials
Corticoids
corticosteroid
Double-Blind Method
Drug dosages
Eosinophil
Eosinophilia
Eosinophilia - drug therapy
Eosinophilia - immunology
Female
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Hematologic and hematopoietic diseases
Humans
Hypereosinophilic Syndrome - drug therapy
Hypereosinophilic Syndrome - immunology
Immunopathology
interleukin-5
Laboratories
Leukocytes (eosinophilic)
Male
Medical sciences
Medical treatment
Middle Aged
Monoclonal antibodies
monoclonal antibody
Other diseases. Hematologic involvement in other diseases
Pain
Population
Prednisone
Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
Time
Toxicity
Young Adult
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Summary:Background Hypereosinophilic syndromes (HESs) are chronic disorders that require long-term therapy to suppress eosinophilia and clinical manifestations. Corticosteroids are usually effective, yet many patients become corticosteroid refractory or develop corticosteroid toxicity. Mepolizumab, a humanized monoclonal anti-IL-5 antibody, showed corticosteroid-sparing effects in a double-blind, placebo-controlled study of FIP1L1/PDGFRA -negative, corticosteroid-responsive subjects with HESs. Objective We evaluated long-term safety and efficacy of mepolizumab (750 mg) in HES. Methods MHE100901 is an open-label extension study. The primary end point was the frequency of adverse events (AEs). Optimal dosing frequency, corticosteroid-sparing effect of mepolizumab, and development of antimepolizumab antibodies were also explored. Results Seventy-eight subjects received 1 to 66 mepolizumab infusions each (including mepolizumab infusions received in the placebo-controlled trial). Mean exposure was 251 weeks (range, 4-302 weeks). The most common dosing interval was 9 to 12 weeks. The incidence of AEs was 932 events per 100 subject-years in the first year, declining to 461 events per 100 subject-years after 48 months. Serious AEs, including 1 death, were reported by the investigator as possibly due to mepolizumab in 3 subjects. The median daily prednisone dose decreased from 20.0 to 0 mg in the first 24 weeks. The median average daily dose for all subjects over the course of the study was 1.8 mg. Sixty-two percent of subjects were prednisone free without other HES medications for ≥12 consecutive weeks. No neutralizing antibodies were detected. Twenty-four subjects withdrew before study completion for death (n = 4), lack of efficacy (n = 6), or other reasons. Conclusion Mepolizumab was well tolerated and effective as a long-term corticosteroid-sparing agent in PDGFRA -negative HES.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2012.07.055