期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 125, 期 4, 页码 803-813出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2009.11.048
关键词
Anti-IL-5; hypereosinophilic syndrome; IL-5; mepolizumab
资金
- GlaxoSmithKline [MHE100185, MHE100901, SB-240563/001, SB-240563/006, SB-240563/036, SB-240563/046, GSK 110184]
- Novartis
- Schering-Plough
- Fujisawa
- GlaxoSmithKline
- Bencard
- Stallergenes
- ALK-Abello
- Allergopharma
- Pharmacia
- DPC Biermann
- Aventis
- Almirall
- Leo
- Galderma
- Switch Biotech
- National Institutes of Health National Institute of Allergy
- Infections Diseases and National Heart, Lung, and Blood Institute
The hypereosinophilic syndromes (HESs) are a heterogeneous group of diseases characterized by peripheral blood eosinophilia with end-organ damage and varying in severity from nonspecific symptoms to life-threatening. Treatment objectives are a safe reduction of blood and tissue eosinophil levels and prevention of eosinophil-mediated tissue damage. Current treatment of patients with HESs, who lack the FIP-1-like 1-platelet-derived growth factor receptor a (FIPILI-PDGFRA) fusion gene, is mainly systemic corticosteroid therapy. Eosinophil development from hematopoietic progenitor cells is regulated by IL-5, which influences maturation, differentiation, mobilization, activation, and survival. Consequently, inhibiting IL-5 is a logical therapeutic objective for patients with HESs or selected patients with asthma. Mepolizumab is a fully humanized anti IL-5 monoclonal IgG(I) antibody that binds to free IL-5 with high affinity and specificity to prevent IL-5 from associating with the IL-5 receptor complex a-chain on the surface of eosinophils. In clinical trials with patients with HESs, mepolizumab reduced blood eosinophil counts and the maintenance corticosteroid dose and had no major safety concerns. Mepolizumab reduced airway and blood eosinophils and prevented asthma exacerbations. Thus, mepolizumab may be effective for long-term treatment of patients with selected eosinophilic disorders. (J Allergy Clin Immunol 2010;125:803-13.)
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