title: Prevention of clinically important deteriorations in COPD with umeclidinium/vilanterol.
abstract: BACKGROUND
  Minimizing the risk of disease progression and exacerbations is the key goal of COPD management, as these are well-established indicators of poor COPD prognosis. We developed a novel composite end point assessing three important aspects (lung function, health status, and exacerbations) of worsening in COPD. The objective was to determine whether dual bronchodilation with umeclidinium/vilanterol (UMEC/VI) reduces clinically important deteriorations (CIDs) in COPD versus placebo or bronchodilator monotherapy.
  
  
  METHODS
  This study is a post hoc analysis of two 24-week trials comparing UMEC/VI 62.5/25 µg with UMEC 62.5 µg, VI 25 µg, or placebo (Study A; NCT01313650), or UMEC/VI 62.5/25 µg with tiotropium (TIO) 18 µg (Study B; NCT01777334) in patients with symptomatic COPD, without a history of frequent exacerbations. Deterioration was assessed as the time to a first CID, a composite measure defined as a decrease of ≥100 mL in trough forced expiratory volume in 1 second or ≥4-unit increase in St George's Respiratory Questionnaire total score or an on-treatment moderate-to-severe COPD exacerbation.
  
  
  RESULTS
  In Study A, fewer patients experienced a first CID with UMEC/VI (44%) versus UMEC (50%), VI (56%), and placebo (75%). The risk of a first CID was reduced with UMEC/VI (hazard ratio [HR]: 0.37 [95% confidence interval, CI: 0.30, 0.45]), UMEC (HR: 0.46 [95% CI: 0.38, 0.56]), and VI (HR: 0.55 [95% CI: 0.45, 0.66]; all P<0.001) versus placebo, and with UMEC/VI versus UMEC (HR: 0.80 [95% CI: 0.65, 0.97]; P<0.05) and versus VI (HR: 0.67 [95% CI: 0.55, 0.81]; P<0.001). In Study B, fewer patients experienced a first CID with UMEC/VI (41%) versus TIO (59%). UMEC/VI reduced the risk of a first composite CID by 43% versus TIO (HR: 0.57 [95% CI: 0.47, 0.69]; P<0.001).
  
  
  CONCLUSIONS
  This exploratory analysis, using a new assessment of clinical deterioration in COPD, revealed that a majority of symptomatic patients with low exacerbation risk experienced a deterioration during the 24-week study periods. UMEC/VI reduces the risk of a first CID versus placebo or bronchodilator monotherapy.
authors.affiliation: Medicines Evaluation Unit, University of Manchester, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: Dave
authors.initials: D
authors.lastname: Singh
authors.affiliation: Division of Respiratory Medicine, Women's College Hospital, University of Toronto, ON, Canada.
authors.forename: M Reza
authors.initials: MR
authors.lastname: Maleki-Yazdi
authors.affiliation: Precise Approach LTD, London UK.
authors.forename: Lee
authors.initials: L
authors.lastname: Tombs
authors.affiliation: Respiratory Medical Franchise, GSK, Research Triangle Park, NC, USA.
authors.forename: Ahmar
authors.initials: A
authors.lastname: Iqbal
authors.affiliation: Respiratory Medicines Development Centre, GSK, Stockley Park, Middlesex, UK.
authors.forename: William A
authors.initials: WA
authors.lastname: Fahy
authors.affiliation: Respiratory Medicines Development Centre, GSK, Stockley Park, Middlesex, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Naya
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000368:Aged; D001592:Benzyl Alcohols / Q000008:administration & dosage* / Q000009:adverse effects; D002722:Chlorobenzenes / Q000008:administration & dosage* / Q000009:adverse effects; D017326:Clinical Trials, Phase III as Topic; D018450:Disease Progression; D018572:Disease-Free Survival; D004338:Drug Combinations; D005260:Female; D005541:Forced Expiratory Volume; D006304:Health Status; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D018727:Muscarinic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D010627:Phenethylamines / Q000008:administration & dosage* / Q000009:adverse effects; D011437:Propylamines / Q000008:administration & dosage* / Q000009:adverse effects; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D011812:Quinuclidines / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D013147:Spirometry; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D014797:Vital Capacity
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001592:Benzyl Alcohols; D002722:Chlorobenzenes; D004338:Drug Combinations; C573971:GSK573719; D018727:Muscarinic Antagonists; D010627:Phenethylamines; D011437:Propylamines; D011812:Quinuclidines; C550468:vilanterol; C011412:bronchodilat
keywords: COPD; UMEC/VI; airway stability; deterioration