Anti-interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes.
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.
Garrett
Jennifer K
JK
Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Jameson
Sean C
SC
Thomson
Blythe
B
Collins
Margaret H
MH
Wagoner
Lynne E
LE
Freese
Debbie K
DK
Beck
Lisa A
LA
Boyce
Joshua A
JA
Filipovich
Alexandra H
AH
Villanueva
Joyce M
JM
Sutton
Steven A
SA
Assa'ad
Amal H
AH
Rothenberg
Marc E
ME
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D004359:Drug Therapy, Combination; D004804:Eosinophils / Q000276:immunology; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000188:drug therapy* / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005938:Glucocorticoids; D015848:Interleukin-5; C434107:mepolizumab