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-α (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-α; 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.

Key words:

• Corticosteroids
• Hypereosinophilic syndrome
• Mepolizumab
• Side-effects

Transparency

Declaration of funding

The three cases presented in the current manuscript were taken from larger studies sponsored by GlaxoSmithKline, including protocol MHE100185, a multicenter, randomized, placebo-controlled study of mepolizumab in hypereosinophilic syndrome that has been published (Rothenberg ME, Klion AD, Roufosse FE, Kahn JE, Weller PF, Simon HU, Schwartz LB, Rosenwasser LJ, Ring J, Griffin EF, Haig AE, Frewer PIH, Parkin JM, Gleich GJ, on behalf of the Mepolizumab HES Study Group. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med 2008;358:1215–28); and protocol MHE100901, a follow-up open-label study of mepolizumab in hypereosinophilic syndrome, and the program for the compassionate use of mepolizumab in hypereosinophilic syndrome (protocol MHE104317 in the US, Canada and France and the Named Patient Supply program in all other regions. No additional funding was provided to the authors of the current report.

Declaration of financial/other relationships

L.B.S., J.S., and A.S. have disclosed that they participated in the above-mentioned GlaxoSmithKline-sponsored studies as the principal investigators of their sites. They have stated that no other significant financial, employment or other relationship exists between the authors and GlaxoSmithKline. Virginia Commonwealth University receives royalties from Phadia (Uppsala, Sweden) for the tryptase assay and shares them with the inventor, L.B.S.

Acknowledgments

Editorial support in the form of initial literature search and writing assistance with outline and draft development, assembling tables and figures, collating author comments, grammatical editing, and referencing was provided by Dr Elaine F. Griffin at Evidence Scientific Solutions which was funded by GlaxoSmithKline.