title: Effects of benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia.
abstract: BACKGROUND
  Many asthmatic patients exhibit sputum eosinophilia associated with exacerbations. Benralizumab targets eosinophils by binding IL-5 receptor α, inducing apoptosis through antibody-dependent cell-mediated cytotoxicity.
  
  
  OBJECTIVE
  We sought to evaluate the safety of benralizumab in adults with eosinophilic asthma and its effects on eosinophil counts in airway mucosal/submucosal biopsy specimens, sputum, bone marrow, and peripheral blood.
  
  
  METHODS
  In this multicenter, double-blind, placebo-controlled phase I study, 13 subjects were randomized to single-dose intravenous placebo or 1 mg/kg benralizumab (day 0; cohort 1), and 14 subjects were randomized to 3 monthly subcutaneous doses of placebo or 100 or 200 mg of benralizumab (days 0, 28, and 56; cohort 2). Cohorts 1 and 2 were consecutive.
  
  
  RESULTS
  The incidence of adverse events was similar between groups. No serious adverse events related to benralizumab occurred. In cohort 1 intravenous benralizumab produced a median decrease from baseline of 61.9% in airway mucosal eosinophil counts (day 28; placebo: +19.6%; P = .28), as well as an 18.7% decrease (day 21) in sputum and a 100% decrease (day 28) in blood counts. Eosinophils were not detectable in bone marrow of benralizumab-treated subjects (day 28, n = 4). In cohort 2 subcutaneous benralizumab demonstrated a combined (100 + 200 mg) median reduction of 95.8% in airway eosinophil counts (day 84; placebo, 46.7%; P = .06), as well as an 89.9% decrease (day 28) in sputum and a 100% decrease (day 84) in blood counts.
  
  
  CONCLUSIONS
  Single-dose intravenous and multiple-dose subcutaneous benralizumab reduced eosinophil counts in airway mucosa/submucosa and sputum and suppressed eosinophil counts in bone marrow and peripheral blood. The safety profile supports further development. Additional studies are needed to assess the clinical benefit in asthmatic patients.
authors.affiliation: Faculté de médecine, département de médecine, Université Laval, Quebec City, Quebec, Canada. Electronic address: michel.laviolette@med.ulaval.ca.
authors.forename: Michel
authors.initials: M
authors.lastname: Laviolette
authors.forename: David L
authors.initials: DL
authors.lastname: Gossage
authors.forename: Gail
authors.initials: G
authors.lastname: Gauvreau
authors.forename: Richard
authors.initials: R
authors.lastname: Leigh
authors.forename: Ron
authors.initials: R
authors.lastname: Olivenstein
authors.forename: Rohit
authors.initials: R
authors.lastname: Katial
authors.forename: William W
authors.initials: WW
authors.lastname: Busse
authors.forename: Sally
authors.initials: S
authors.lastname: Wenzel
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wu
authors.forename: Vivekananda
authors.initials: V
authors.lastname: Datta
authors.forename: Roland
authors.initials: R
authors.lastname: Kolbeck
authors.forename: Nestor A
authors.initials: NA
authors.lastname: Molfino
mesh_terms: D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D001491:Basophils; D001853:Bone Marrow / Q000473:pathology; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009504:Neutrophils; D053649:Receptors, Interleukin-5 / Q000037:antagonists & inhibitors; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology*; D013183:Sputum / Q000166:cytology* / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018927:Anti-Asthmatic Agents; D061067:Antibodies, Monoclonal, Humanized; D053649:Receptors, Interleukin-5; C571386:benralizumab
keywords: ADCC; AE; ATP; According to protocol; Adverse event; Antibody-dependent cell-mediated cytotoxicity; C-reactive protein; CPK; CRP; Creatine phosphokinase; Eosinophils; H&E; Hematoxylin and eosin; ICS; IL-5; IL-5 receptor; IL-5 receptors; IL-5R; IQR; Inhaled corticosteroid; Interquartile range; SABA; Short-acting β(2)-agonist; antibody-dependent cell-mediated cytotoxicity; asthma