Reductions in eosinophil biomarkers by benralizumab in patients with asthma

Abstract Background Eosinophilic inflammation is frequently associated with increased asthma severity. Benralizumab is a humanized, afucosylated, anti–interleukin-5Rα monoclonal antibody that selectively depletes eosinophils and basophils through enhanced antibody-dependent cell-mediated cytotoxicit...

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Bibliographic Details
Published in:Respiratory medicine 2016-02, Vol.111, p.21-29
Main Authors: Pham, Tuyet-Hang, Damera, Gautam, Newbold, Paul, Ranade, Koustubh
Format: Article
Language:English
Subjects:
Adult
Aged
Antibodies, Monoclonal, Humanized - therapeutic use
Antibody-Dependent Cell Cytotoxicity
Asthma
Asthma - blood
Asthma - drug therapy
Asthma - immunology
Benralizumab
Biomarker
Biomarkers
Biomarkers - blood
Chemokines
Clinical trials
Cytokines
Cytotoxicity
Double-Blind Method
Eosinophil
Eosinophil Cationic Protein - blood
Eosinophil-Derived Neurotoxin - blood
Eosinophils - drug effects
Eosinophils - immunology
Eosinophils - pathology
Family medical history
Female
Gangrene
Humans
IL-5
Inflammation
Interleukin-5 - blood
Interleukin-5 - immunology
Male
Middle Aged
Proteins
Pulmonary/Respiratory
Studies
Tumor necrosis factor-TNF
Young Adult
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Summary:Abstract Background Eosinophilic inflammation is frequently associated with increased asthma severity. Benralizumab is a humanized, afucosylated, anti–interleukin-5Rα monoclonal antibody that selectively depletes eosinophils and basophils through enhanced antibody-dependent cell-mediated cytotoxicity. Objective To study effects of benralizumab on eosinophil counts and activity following administration to asthma patients. Methods Sera were collected from asthma patients enrolled in two clinical studies. Placebo or benralizumab was subcutaneously administered to patients in Phase I (100 or 200 mg, multiple doses; N  = 14; NCT00659659) and Phase IIa (25, 100, or 200 mg every 4 weeks; N  = 24; NCT00783289) studies. Sera were also collected from healthy volunteers ( N  = 20) for comparison. Blood eosinophils, IL-5, eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), eotaxin/chemokine (C–C motif) 11 (CCL11), eotaxin-2/CCL24, tumor necrosis factor (TNF), and interferon-γ (IFN-γ) were measured at baseline and post-treatment. Results Increased EDN concentrations were observed in sera of patients from both studies relative to healthy volunteers ( p  
ISSN:0954-6111
1532-3064
DOI:10.1016/j.rmed.2016.01.003