title: Blood Eosinophils and Response to Maintenance Chronic Obstructive Pulmonary Disease Treatment. Data from the FLAME Trial.
abstract: Post hoc analyses suggest that blood eosinophils have potential as a predictive biomarker of inhaled corticosteroid efficacy in the management of chronic obstructive pulmonary disease (COPD).
  
  
  
  We prospectively investigated the value of blood eosinophils as a predictor of responsiveness to an inhaled corticosteroid/long-acting β2-agonist combination versus a long-acting β2-agonist/long-acting muscarinic antagonist combination for exacerbation prevention.
  
  
  
  We conducted prespecified analyses of data from the FLAME (Effect of Indacaterol Glycopyronium vs Fluticasone Salmeterol on COPD Exacerbations) study, which compared once-daily long-acting β2-agonist/long-acting muscarinic antagonist indacaterol/glycopyrronium 110/50 μg with twice-daily long-acting β2-agonist/inhaled corticosteroid salmeterol/fluticasone combination 50/500 μg in patients with one or more exacerbations in the preceding year. Subsequent post hoc analyses were conducted to address further cutoffs and endpoints.
  
  
  
  We compared treatment efficacy according to blood eosinophil percentage (<2% and ≥2%, <3% and ≥3%, and <5% and ≥5%) and absolute blood eosinophil count (<150 cells/μl, 150 to <300 cells/μl, and ≥300 cells/μl). Indacaterol/glycopyrronium was significantly superior to salmeterol/fluticasone for the prevention of exacerbations (all severities, or moderate or severe) in the <2%, ≥2%, <3%, <5%, and <150 cells/μl subgroups, and at no cutoff was salmeterol/fluticasone superior to indacaterol/glycopyrronium. Furthermore, the rate of moderate or severe exacerbations did not increase with increasing blood eosinophils. The incidence of pneumonia was higher in patients receiving salmeterol/fluticasone than indacaterol/glycopyrronium in both the <2% and ≥2% subgroups.
  
  
  
  Our prospective analyses indicate that indacaterol/glycopyrronium provides superior or similar benefits over salmeterol/fluticasone regardless of blood eosinophil levels in patients with COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01782326).
authors.affiliation: 1 Service de Pneumologie AP-HP, University Paris Descartes (EA2511), Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Roche
authors.affiliation: 2 Asthma and Airway Centre, University Health Network and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Chapman
authors.affiliation: 3 Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg, Marburg, Germany.
authors.forename: Claus F
authors.initials: CF
authors.lastname: Vogelmeier
authors.affiliation: 4 Department of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg and Translational Lung Research Center Heidelberg, German Center for Lung Research, Heidelberg, Germany.
authors.forename: Felix J F
authors.initials: FJF
authors.lastname: Herth
authors.affiliation: 5 Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Chau
authors.initials: C
authors.lastname: Thach
authors.affiliation: 5 Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Robert
authors.initials: R
authors.lastname: Fogel
authors.affiliation: 6 Novartis Sverige AB, Täby, Sweden.
authors.forename: Petter
authors.identifier: 0000-0002-3913-3914
authors.initials: P
authors.lastname: Olsson
authors.affiliation: 7 Novartis Pharma AG, Basel, Switzerland; and.
authors.forename: Francesco
authors.initials: F
authors.lastname: Patalano
authors.affiliation: 5 Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Donald
authors.initials: D
authors.lastname: Banerji
authors.affiliation: 8 National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Jadwiga A
authors.initials: JA
authors.lastname: Wedzicha
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000627:therapeutic use; D000368:Aged; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004804:Eosinophils / Q000187:drug effects; D005260:Female; D000068297:Fluticasone-Salmeterol Drug Combination / Q000627:therapeutic use; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000188:drug therapy; D015363:Quinolones / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D015415:Biomarkers; D000068297:Fluticasone-Salmeterol Drug Combination; D007189:Indans; D015363:Quinolones; C510790:indacaterol
keywords: QVA149; bronchodilation; chronic obstructive pulmonary disease; exacerbations; inhaled corticosteroids