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

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 beta(2)-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 mu g versus placebo (1 year); indacaterol 150 mg and 300 mg versus placebo (6 months); and indacaterol 150 mg versus placebo (6 months). All treatments were administered oncedaily. 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 mu g [n = 746], indacaterol 300 mu g [n = 819], placebo [n = 1151]). Both indacaterol doses 150 and 300 mg 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 mg 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 mg (Least squares mean treatment differences: Month 3 = 170 mL; Month 6 = 160 mL) and 300 mg (170 mL at both time-points; all p < 0.001). Conclusions: In this pooled analysis, both indacaterol doses, 150 and 300 mg, 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. (C) 2014 Elsevier Ltd. All rights reserved.