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

• Published in: Journal of allergy and clinical immunology Vol. 131; no. 2; pp. 461 - 467.e5
• Main Authors: Roufosse, Florence E., Kahn, Jean-Emmanuel, Gleich, Gerald J., Schwartz, Lawrence B., Singh, Anish D., Rosenwasser, Lanny J., Denburg, Judah A., Ring, Johannes, Rothenberg, Marc E., Sheikh, Javed, Haig, Ann E., Mallett, Stephen A., Templeton, Deborah N., Ortega, Hector G., Klion, Amy D.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.02.2013; Elsevier; Elsevier Limited
• Subjects: Adolescent; adrenal cortex hormones; 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; average daily intake; Biological and medical sciences; Blood; Cancer; Clinical trials; Corticoids; corticosteroid; death; 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; neutralizing antibodies; Other diseases. Hematologic involvement in other diseases; Pain; patients; Population; Prednisone; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; therapeutics; Time; Toxicity; Young Adult; L-HES; AE; SAE; HES; corticosteroid; SEER; monoclonal antibody; Eosinophil; AITL; interleukin-5; AEC; Absolute eosinophil count; Angioimmunoblastic T cell lymphoma; Hypereosinophilic syndromes; Adverse event; Lymphocytic variant HES; Surveillance Epidemiology and End Results; Serious adverse event; Corticosteroid; Immunopathology; Toxicity; Cytokine; Granulocyte; Hemopathy; Monoclonal antibody; Long term; Mepolizumab; Immunology; Interleukin 5; Treatment; Hypereosinophilic syndrome
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2012.07.055

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. We evaluated long-term safety and efficacy of mepolizumab (750 mg) in HES. 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. 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. Mepolizumab was well tolerated and effective as a long-term corticosteroid-sparing agent in PDGFRA-negative HES.