Anti-interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes.

Abstract

BACKGROUND:

IL-5 is a cytokine critically involved in regulating several aspects of eosinophils including their production, activation, and tissue recruitment. As such, IL-5 may be involved in the pathogenesis of hypereosinophilic syndromes, a group of poorly treated diverse disorders characterized by sustained peripheral blood and/or tissue eosinophilia.

OBJECTIVE:

We aimed to assess the safety and efficacy of a humanized blocking monoclonal antibody against IL-5 (mepolizumab) in patients with several forms of hyper-eosinophilic syndromes.

METHODS:

We performed an open-label trial of anti-IL-5 in which 3 intravenous doses (10 mg/kg, maximum 750 mg) were administered at 4-week intervals to 4 patients with hypereosinophilic syndromes (defined by peripheral blood and/or tissue eosinophilia). The effects of treatment on safety, eosinophil levels (in peripheral blood and/or diseased tissue), pulmonary function, and quality of life were measured over a 28-week period.

RESULTS:

Anti-IL-5 was well tolerated in all patients and lowered peripheral blood eosinophil counts despite ongoing systemic glucocorticoid therapy. The decline in circulating eosinophil counts was sustained for at least 12 weeks after the last dose of anti-IL-5. In addition, anti-IL-5 improved clinical and quality of life measurements. In one patient with striking tissue eosinophilia (eosinophilic esophagitis), anti-IL-5 resulted in a 10-fold reduction in tissue eosinophil levels.

CONCLUSIONS:

These results suggest that anti-IL-5 is safe, effective in lowering eosinophil levels, and has potential glucocorticoid-sparing effects in patients with a variety of hyper-eosinophilic syndromes. As such, anti-IL-5 may have significant therapeutic potential for hypereosinophilic syndromes.

• Authors: Jennifer K Garrett, Sean C Jameson, Blythe Thomson, Margaret H Collins, Lynne E Wagoner, Debbie K Freese, Lisa A Beck, Joshua A Boyce, Alexandra H Filipovich, Joyce M Villanueva, Steven A Sutton, Amal H Assa'ad, Marc E Rothenberg
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 113 Issue 1 Pg. 115-9 (Jan 2004) ISSN: 0091-6749 [Print] United States
• PMID: 14699394 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Glucocorticoids
• Interleukin-5
• mepolizumab

Topics

• Adolescent
• Adult
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized
• Drug Therapy, Combination
• Eosinophils (immunology)
• Female
• Glucocorticoids (therapeutic use)
• Humans
• Hypereosinophilic Syndrome (drug therapy, immunology)
• Interleukin-5 (immunology)
• Leukocyte Count
• Male
• Middle Aged