title: Pooled subpopulation analyses of the effects of roflumilast on exacerbations and lung function in COPD.
abstract: BACKGROUND
  This post-hoc analysis examined the impact of roflumilast on chronic obstructive pulmonary disease (COPD) exacerbations and lung function in patients with COPD who received concomitant long-acting β2-agonists (LABA) with or without prior inhaled corticosteroid (ICS) and the influence of various demographic and clinical characteristics on these outcomes.
  
  
  METHODS
  Data were pooled from 2 double-blind, placebo-controlled, 52-week studies of once-daily roflumilast 500 μg in patients with COPD. Endpoints were mean rate of exacerbations and change from baseline in pre- and postbronchodilator FEV1.
  
  
  RESULTS
  In this pooled analysis (N = 3091), addition of roflumilast to LABAs for 1 year in patients who discontinued ICS prior to study entry (n = 945) significantly reduced the risk of COPD exacerbations vs. placebo by 19.2% (p < 0.05) and significantly improved pre- and postbronchodilator FEV1 by 40 mL and 34 mL, respectively (both, p < 0.01). Similar improvements were observed in patients who received concomitant LABAs but were not taking ICS prior to study entry (n = 597). A significant reduction in COPD exacerbation risk with roflumilast vs. placebo was observed regardless of age or smoking status, and in patients who had severe or very severe COPD. Significantly improved lung function was observed with roflumilast in all the subgroups (p < 0.05), with the exception of patients with moderate COPD.
  
  
  CONCLUSIONS
  Roflumilast reduced exacerbation rates and improved lung function in patients with COPD who received concomitant LABA, regardless of prior ICS use, and across various patient subgroups regardless of age and smoking status.
  
  
  BACKGROUND
  NCT00297102 (M2-124) and NCT00297115 (M2-125).
authors.affiliation: Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: hanania@bcm.edu.
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Hanania
authors.affiliation: University of Liverpool, Liverpool L69 3BX, England, UK.
authors.forename: Peter M A
authors.initials: PM
authors.lastname: Calverley
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL 35233, USA.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Dransfield
authors.affiliation: North Shore Medical Arts, Great Neck, NY 11021, USA.
authors.forename: Jill P
authors.initials: JP
authors.lastname: Karpel
authors.affiliation: Takeda Pharmaceuticals International GmbH, Zürich, Switzerland.
authors.forename: Manja
authors.initials: M
authors.lastname: Brose
authors.affiliation: Forest Research Institute, Jersey City, NJ 07311, USA.
authors.forename: Haiyuan
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Takeda Pharmaceuticals International GmbH, Zürich, Switzerland.
authors.forename: Udo-Michael
authors.initials: UM
authors.lastname: Goehring
authors.affiliation: Forest Research Institute, Jersey City, NJ 07311, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Rowe
mesh_terms: D000208:Acute Disease; D000284:Administration, Oral; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage; D000631:Aminopyridines / Q000008:administration & dosage*; D001549:Benzamides / Q000008:administration & dosage*; D001993:Bronchodilator Agents / Q000008:administration & dosage; D003521:Cyclopropanes / Q000008:administration & dosage; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D058988:Phosphodiesterase 4 Inhibitors / Q000008:administration & dosage*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D012907:Smoking / Q000503:physiopathology
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000631:Aminopyridines; D001549:Benzamides; D001993:Bronchodilator Agents; D003521:Cyclopropanes; D003692:Delayed-Action Preparations; D058988:Phosphodiesterase 4 Inhibitors; C424423:Roflumilast
keywords: Chronic obstructive pulmonary disease; Exacerbation; Inhaled corticosteroids; Long-acting β(2)-agonists; Lung function; Roflumilast