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 alpha (FIP1L1-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(1) antibody that binds to free IL-5 with high affinity and specificity to prevent IL-5 from associating with the IL-5 receptor complex alpha-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.
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