Mepolizumab as a corticosteroid-sparing agent in lymphocytic variant hypereosinophilic syndrome.
BACKGROUND
Mepolizumab, a monoclonal anti-IL-5 antibody, is an effective corticosteroid-sparing agent for patients with Fip1-like 1/platelet-derived growth factor receptor α fusion (F/P)-negative hypereosinophilic syndrome (HES). Lymphocytic variant hypereosinophilic syndrome (L-HES) is characterized by marked overproduction of IL-5 by dysregulated T cells.


OBJECTIVE
To determine whether patients with L-HES respond to mepolizumab in terms of corticosteroid tapering and eosinophil depletion to the same extent as corticosteroid-responsive F/P-negative patients with HES and a normal T-cell profile.


METHODS
Patients enrolled in the mepolizumab trial were evaluated for L-HES on the basis of T-cell phenotyping and T-cell receptor gene rearrangement patterns, and their serum thymus-and-activation-regulated chemokine (TARC) levels were measured. Response to treatment was compared in patient subgroups based on results of these analyses.


RESULTS
Lymphocytic variant HES was diagnosed in 13 of 63 patients with HES with complete T-cell assessments. The ability to taper corticosteroids on mepolizumab was similar in patients with L-HES and those with a normal T-cell profile, although a lower proportion of patients with L-HES maintained eosinophil levels below 600/μL. Increased serum TARC levels (>1000 pg/mL) had no significant impact on the ability to reduce corticosteroid doses, but a lower proportion of patients with elevated TARC achieved eosinophil control on mepolizumab.


CONCLUSIONS
Mepolizumab is an effective corticosteroid-sparing agent for patients with L-HES. In some cases however, eosinophil levels remain above 600/μL, suggesting incomplete neutralization of overproduced IL-5 or involvement of other eosinophilopoietic factors.
Roufosse
Florence
F
Department of Internal Medicine, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium. froufoss@ulb.ac.be
de Lavareille
Aurore
A
Schandené
Liliane
L
Cogan
Elie
E
Georgelas
Ann
A
Wagner
Lori
L
Xi
Liqiang
L
Raffeld
Mark
M
Goldman
Michel
M
Gleich
Gerald J
GJ
Klion
Amy
A
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D017252:CD3 Complex / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D054414:Chemokine CCL17 / Q000097:blood; D004311:Double-Blind Method; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000188:drug therapy* / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology / Q000378:metabolism*; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016896:Treatment Outcome; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C106230:CCL17 protein, human; D017252:CD3 Complex; D015704:CD4 Antigens; D054414:Chemokine CCL17; C508599:IL5 protein, human; D015848:Interleukin-5; C434107:mepolizumab; D011241:Prednisone
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