In patients with a history of exacerbation during the previous year, indacaterol-glycopyrronium was more effective than salmeterol-fluticasone in preventing COPD exacerbations. This according to the results of a 52-week, randomized, double-blind, noninferiority trial of patients who had COPD with a history of at least 1 exacerbation during the previous year and who were randomly assigned to either the indacaterol-glycopyrronium group (n=1,680) or the salmeterol-fluticasone group (n=1,682). Researchers found:

• Annual rate of all COPD exacerbations was 11% lower in the indacaterol-glycopyrronium group vs the salmeterol-fluticasone group (rate ratio, 0.89).

• The indacaterol-glycopyrronium group has a longer time to first exacerbation than did the salmeterol-fluticasone group (71 days vs 51 days; HR=0.84), representing a 16% lower risk.

• Annual rate of moderate to severe exacerbations was lower in the indacaterol-glycopyrronium group vs the salmeterol-fluticasone group (0.98 vs 1.19; RR=0.83), and the time to the first moderate or severe exacerbation was longer in the indacaterol-glycopyrronium group vs the salmeterol-fluticasone group (HR=0.78), as was the time to the first severe exacerbation (HR=0.81).

Citation: Wedzicha JA, Banerji D, Chapman KR, et al. Indacaterol-glycopyrronium group versus salmeterol-fluticasone for COPD. [Published online ahead of print May 15, 2016]. N Engl J Med. doi:10.1056/NEJMoa1516385.

Commentary: This important study helps to clarify the place of dual bronchodilator therapy in COPD. Indacaterol-glycopyrronium is a combination of a long-acting beta-agonist (LABA) and a long-acting anti-muscarinic (LAMA). Salmeterol-fluticasone is a combination of a LABA and an inhaled corticosteroid (ICS). Currently the standard guidelines for COPD, the GOLD guidelines, recommend that first-line treatment for GOLD Stage A is short-acting bronchodilator; for GOLD Stage B, LAMA or LABA; for GOLD Stage C, combination therapy with ICS plus a LABA or a LAMA with alternative choices being combination of LABA/LAMA or bronchodilator (LABA or LAMA) and PDE-4 inhibitor. The relative benefit of the ICS component, while the foundation for therapy in asthma, has been debated for COPD, and is known to cause a small but significant increase in community acquired pneumonia. The relative benefit of combination bronchodilator therapy vs combination ICS/LABA has also been debated, with few large studies to guide us. This study provides evidence that therapy of COPD with combination LABA/LAMA is superior to ICS/LABA in decreasing exacerbations, and so may be considered as first-line therapy in patients with exacerbations. —Neil Skolnik, MD