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Current strategies in the management of hypereosinophilic syndrome, including mepolizumab.

Abstract：

BACKGROUND:Patients with hypereosinophilic syndrome (HES) vary considerably in their clinical presentation with regard to the severity and pattern of end-organ involvement. Clinical manifestations range from nonspecific symptoms to life-threatening, multisystem damage caused by eosinophil infiltration and local release of proinflammatory mediators and toxic granule products from these invading cells. The primary objective of treatment is to reduce blood and tissue eosinophilia and prevent eosinophil-mediated tissue damage as safely as possible. Systemic corticosteroids, such as prednisone, are first-line therapy for the management of patients with symptomatic HES who lack the Fip1-like 1-platelet-derived growth factor receptor-alpha (FIP1L1-PDGFRA) gene fusion mutation. The tyrosine kinase inhibitor, imatinib, is first-line treatment for FIP1L1-PDGFRA-positive patients). Because of the toxicity and serious side-effects that can occur with oral corticosteroids, alternative therapies may need to be introduced to reduce the cumulative corticosteroid exposure while maintaining disease control. SCOPE:Among corticosteroid-sparing agents are cytotoxic drugs and interferon-alpha; anti-interleukin-5 (IL-5) monoclonal antibodies are also currently under investigation for the treatment of HES. This manuscript reviews the available treatments for HES and the range of side-effects associated with long-term corticosteroid use, and then focuses on the anti-IL-5 monoclonal antibodies, mepolizumab and reslizumab. Of these, only mepolizumab has been studied in a randomized, placebo-controlled trial. Literature search methodology utilized www.pubmed.gov and www.clinicaltrials.gov with search terms including hypereosinophilic syndrome and corticosteroid side-effects coupled with search terms including eosinophils, mepolizumab and reslizumab through March 2010. FINDINGS:Three case studies are presented that demonstrate the limitations of corticosteroid therapy in terms of tolerability and quality of life, and the subsequent use of mepolizumab as a corticosteroid-sparing agent in these individuals. CONCLUSION:Targeted eosinophil-directed therapy with an anti-IL-5 neutralizing monoclonal antibody reduced the need for corticosteroids in these three HES patients without disease exacerbations.

journal_name

Curr Med Res Opin

journal_title

Current medical research and opinion

authors

Schwartz LB,Sheikh J,Singh A

doi

10.1185/03007995.2010.493132

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

1933-46

issue

eissn

0300-7995

issn

1473-4877

journal_volume

pub_type

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Current strategies in the management of hypereosinophilic syndrome, including mepolizumab.