title: Monotherapy with indacaterol once daily reduces the rate of exacerbations in patients with moderate-to-severe COPD: Post-hoc pooled analysis of 6 months data from three large phase III trials.
abstract: BACKGROUND
  In patients with COPD, exacerbations are associated with poor quality of life and may shorten survival. Prevention of exacerbations is, therefore, a key objective in COPD management. Indacaterol, a once-daily ultra-long-acting β2-agonist, has been shown to reduce exacerbations in various studies. This pooled analysis evaluated the effect of indacaterol on exacerbations versus placebo.
  
  
  METHODS
  Six-month data were pooled from three randomized, double-blind, and placebo-controlled studies: indacaterol 300 μg versus placebo (1 year); indacaterol 150 μg and 300 μg versus placebo (6 months); and indacaterol 150 μg versus placebo (6 months). All treatments were administered once daily. Data from other treatment groups were excluded. All three studies enrolled patients aged ≥40 years with moderate-to-severe COPD and smoking history ≥20 pack-years. Time to exacerbation and exacerbation rate were analyzed.
  
  
  RESULTS
  Overall, the pooled data set included 2716 patients (indacaterol 150 μg [n = 746], indacaterol 300 μg [n = 819], placebo [n = 1151]). Both indacaterol doses 150 and 300 μg significantly reduced the COPD exacerbation rates compared with placebo (Rate ratios, RR [95% Confidence Interval, CI]: 0.69 [0.55-0.87], 0.71 [95% CI: 0.57-0.88] respectively; both p = 0.002). Over 6 months, indacaterol 150 and 300 μg also significantly prolonged the time to first moderate-to-severe exacerbation versus placebo (Hazard ratios, HR [95% CI]: 0.74: [0.59-0.93], p = 0.009; 0.73 [0.59-0.90], p = 0.004, respectively). At months 3 and 6, clinically relevant improvements in lung function versus placebo were observed with indacaterol 150 μg (Least squares mean treatment differences: Month 3 = 170 mL; Month 6 = 160 mL) and 300 μg (170 mL at both time-points; all p < 0.001).
  
  
  CONCLUSIONS
  In this pooled analysis, both indacaterol doses, 150 and 300 μg, were associated with significant reductions in exacerbations and significant improvements in bronchodilation versus placebo. The results suggest once-daily indacaterol is an effective treatment option for providing sustained bronchodilation and preventing exacerbations in patients with COPD.
authors.affiliation: Airways Disease Section, National Heart and Lung Institute, Imperial College London, London SW3 6LR, UK. Electronic address: w.wedzicha@imperial.ac.uk.
authors.forename: Jadwiga A
authors.initials: JA
authors.lastname: Wedzicha
authors.affiliation: Pulmonary Department, Mainz University Hospital, Langenbeckstr.1, Mainz, Germany. Electronic address: Roland.Buhl@unimedizin-mainz.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Buhl
authors.affiliation: Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936-1080, USA. Electronic address: davejlawrence@hotmail.com.
authors.forename: David
authors.initials: D
authors.lastname: Lawrence
authors.affiliation: Novartis Horsham Research Centre, Wimblehurst Road, Horsham, West Sussex RH12 5AB, UK. Electronic address: dvdmps@gmail.com.
authors.forename: David
authors.initials: D
authors.lastname: Young
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000627:therapeutic use; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D015363:Quinolones / Q000008:administration & dosage* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D007189:Indans; D015363:Quinolones; C510790:indacaterol
keywords: Bronchodilator; COPD; Exacerbations; Indacaterol; Pooled analysis; β(2)-agonist