title: Umeclidinium/vilanterol as step-up therapy from tiotropium in patients with moderate COPD: a randomized, parallel-group, 12-week study.
abstract: BACKGROUND
  Patients with COPD who remain symptomatic on long-acting bronchodilator monotherapy may benefit from step-up therapy to a long-acting bronchodilator combination. This study evaluated the efficacy and safety of umeclidinium (UMEC)/vilanterol (VI) in patients with moderate COPD who remained symptomatic on tiotropium (TIO).
  
  
  METHODS
  In this randomized, blinded, double-dummy, parallel-group study (NCT01899742), patients (N=494) who were prescribed TIO for ≥3 months at screening (forced expiratory volume in 1 s [FEV1]: 50%-70% of predicted; modified Medical Research Council [mMRC] score ≥1) and completed a 4-week run-in with TIO were randomized to UMEC/VI 62.5/25 µg or TIO 18 µg for 12 weeks. Efficacy assessments included trough FEV1at Day 85 (primary end point), 0-3 h serial FEV1, rescue medication use, Transition Dyspnea Index (TDI), St George's Respiratory Questionnaire (SGRQ), and COPD Assessment Test (CAT). Safety evaluations included adverse events (AEs).
  
  
  RESULTS
  Compared with TIO, UMEC/VI produced greater improvements in trough FEV1(least squares [LS] mean difference: 88 mL at Day 85 [95% confidence interval {CI}: 45-131];P<0.001) and FEV1after 5 min on Day 1 (50 mL [95% CI: 27-72];P<0.001). Reductions in rescue medication use over 12 weeks were greater with UMEC/VI versus TIO (LS mean change: -0.1 puffs/d [95% CI: -0.2-0.0];P≤0.05). More patients achieved clinically meaningful improvements in TDI score (≥1 unit) with UMEC/VI (63%) versus TIO (49%; odds ratio at Day 84=1.78 [95% CI: 1.21-2.64];P≤0.01). Improvements in SGRQ and CAT scores were similar between treatments. The incidence of AEs was similar with UMEC/VI (30%) and TIO (31%).
  
  
  CONCLUSIONS
  UMEC/VI step-up therapy provides clinical benefit over TIO monotherapy in patients with moderate COPD who are symptomatic on TIO alone.
authors.affiliation: Clinical Research Institute of Southern Oregon, Medford, OR.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Kerwin
authors.affiliation: Respiratory Department, GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Kalberg
authors.affiliation: Respiratory Department, GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Galkin
authors.affiliation: Clinical Statistics, GlaxoSmithKline, Stockley Park, Uxbridge, Middlesex.
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Zhu
authors.affiliation: Respiratory Department, GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Church
authors.affiliation: Respiratory Department, GlaxoSmithKline, Stockley Park, Uxbridge, Middlesex, UK.
authors.forename: John H
authors.initials: JH
authors.lastname: Riley
authors.affiliation: Respiratory Department, GlaxoSmithKline, Stockley Park, Uxbridge, Middlesex, UK.
authors.forename: William A
authors.initials: WA
authors.lastname: Fahy
mesh_terms: D000368:Aged; D001118:Argentina; D001592:Benzyl Alcohols / Q000008:administration & dosage* / Q000009:adverse effects; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002722:Chlorobenzenes / Q000008:administration & dosage* / Q000009:adverse effects; D057915:Drug Substitution; D005060:Europe; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D057194:Intention to Treat Analysis; D016018:Least-Squares Analysis; D016015:Logistic Models; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / 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; D020127:Recovery of Function; D013019:South Africa; D011795:Surveys and Questionnaires; D013997:Time Factors; D000069447:Tiotropium Bromide / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014481:United States; D014797:Vital Capacity
chemical_list: D001592:Benzyl Alcohols; D001993:Bronchodilator Agents; D002722:Chlorobenzenes; C573971:GSK573719; D018727:Muscarinic Antagonists; D011812:Quinuclidines; C550468:vilanterol; D000069447:Tiotropium Bromide
keywords: COPD; LABA; LAMA; step-up; tiotropium; umeclidinium/vilanterol