title: 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 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 < 0.05). At baseline, sera EDN concentrations correlated with blood eosinophil counts (rs = 0.5; p < 0.05). Benralizumab reduced blood eosinophil numbers and sera EDN and ECP relative to baseline (p < 0.05). No changes in TNF or IFN-γ were observed, while serum IL-5, eotaxin/CCL11, and eotaxin-2/CCL24 increased after benralizumab administration vs. placebo (p < 0.05).
  
  
  CONCLUSIONS
  In two independent studies, serum IL-5, EDN, and ECP were modulated following benralizumab. Eosinophil depletion after benralizumab also resulted in significant reductions in EDN and ECP concentrations, suggesting that cytotoxic granule proteins were not released after eosinophil reduction.
authors.affiliation: Translational Sciences, MedImmune LLC, Gaithersburg, MD, USA. Electronic address: PhamTu@MedImmune.com.
authors.forename: Tuyet-Hang
authors.initials: TH
authors.lastname: Pham
authors.affiliation: Translational Sciences, MedImmune LLC, Gaithersburg, MD, USA. Electronic address: DameraG@MedImmune.com.
authors.forename: Gautam
authors.initials: G
authors.lastname: Damera
authors.affiliation: Translational Sciences, MedImmune LLC, Gaithersburg, MD, USA. Electronic address: NewboldP@MedImmune.com.
authors.forename: Paul
authors.initials: P
authors.lastname: Newbold
authors.affiliation: Translational Sciences, MedImmune LLC, Gaithersburg, MD, USA. Electronic address: RanadeK@MedImmune.com.
authors.forename: Koustubh
authors.initials: K
authors.lastname: Ranade
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity; D001249:Asthma / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D047150:Eosinophil Cationic Protein / Q000097:blood*; D047208:Eosinophil-Derived Neurotoxin / Q000097:blood*; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D015848:Interleukin-5 / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D015848:Interleukin-5; C571386:benralizumab; D047208:Eosinophil-Derived Neurotoxin; D047150:Eosinophil Cationic Protein
keywords: Asthma; Benralizumab; Biomarker; Eosinophil; IL-5