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

Jadwiga A. Wedzicha1e， Roland Buhle， David Lawrence23e， David Young3e

1Tel.: +44 207 594 7947.

2Tel.: +1 8627788610.

3At the time that this manuscript was written, David Lawrence and David Young were employees of Novartis.

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 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 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.

respiratory medicine

January 2015Volume 109, Issue 1, Pages 105–111

DOI: http://dx.doi.org/10.1016/j.rmed.2014.10.011 |