Anti–interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes☆
Received 11 October 2003; received in revised form 20 October 2003; accepted 12 December 2003.
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.
aDepartment of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
bDepartment of Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
cDepartment of Pediatrics, Mayo Clinic and Foundation, Rochester, Minn, USA
dDepartment of Medicine, Johns Hopkins Asthma and Allergy Center, Johns Hopkins School of Medicine, Baltimore, Md, USA
eDepartment of Medicine, Brigham and Women's Hospital, Department of Pediatrics, Massachusetts General Hospital, Boston, Mass, USA
Reprint requests: Dr Marc E. Rothenberg, Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7028, Cincinnati, OH 45229
☆ Supported in part by the Burroughs Wellcome Fund and the NIH-supported Clinical Research Center and the Translational Research Office at Cincinnati Children's Hospital Medical Center.
ABSTRACT