Indacaterol–Glycopyrronium versus Salmeterol–Fluticasone for COPD

Abstract

BACKGROUNDMost guidelines recommend either a long-acting beta-agonist (LABA) plus an inhaled glucocorticoid or a long-acting muscarinic antagonist (LAMA) as the firstchoice treatment for patients with chronic obstructive pulmonary disease (COPD) who have a high risk of exacerbations. The role of treatment with a LABA-LAMA regimen in these patients is unclear. METHODSWe conducted a 52-week, randomized, double-blind, double-dummy, noninferiority trial. Patients who had COPD with a history of at least one exacerbation during the previous year were randomly assigned to receive, by inhalation, either the LABA indacaterol (110 μg) plus the LAMA glycopyrronium (50 μg) once daily or the LABA salmeterol (50 μg) plus the inhaled glucocorticoid fluticasone (500 μg) twice daily. The primary outcome was the annual rate of all COPD exacerbations. RESULTSA total of 1680 patients were assigned to the indacaterol-glycopyrronium group, and 1682 to the salmeterol-fluticasone group. Indacaterol-glycopyrronium showed not only noninferiority but also superiority to salmeterol-fluticasone in reducing the annual rate of all COPD exacerbations; the rate was 11% lower in the indacaterolglycopyrronium group than in the salmeterol-fluticasone group (3.59 vs. 4.03; rate ratio, 0.89; 95% confidence interval [CI], 0.83 to 0.96; P = 0.003). The indacaterolglycopyrronium group had a longer time to the first exacerbation than did the salmeterol-fluticasone group (71 days [95% CI, 60 to 82] vs. 51 days [95% CI, 46 to 57]; hazard ratio, 0.84 [95% CI, 0.78 to 0.91], representing a 16% lower risk; P<0.001). The annual rate of moderate or severe exacerbations was lower in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (0.98 vs. 1.19; rate ratio, 0.83; 95% CI, 0.75 to 0.91; P<0.001), and the time to the first moderate or severe exacerbation was longer in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (hazard ratio, 0.78; 95% CI, 0.70 to 0.86; P<0.001), as was the time to the first severe exacerbation (hazard ratio, 0.81; 95% CI, 0.66 to 1.00; P = 0.046). The effect of indacaterol-glycopyrronium versus salmeterolfluticasone on the rate of COPD exacerbations was independent of the baseline blood eosinophil count. The incidence of adverse events and deaths was similar in the two groups. The incidence of pneumonia was 3.2% in the indacaterol-glycopyrronium group and 4.8% in the salmeterol-fluticasone group (P = 0.02). CONCLUSIONSIndacaterol-glycopyrronium was more effective than salmeterol-fluticasone in preventing COPD exacerbations in patients with a history of exacerbation during the previous year. (Funded by Novartis; FLAME ClinicalTrials.gov number, NCT01782326.)

The View of the Turkish Thoracic Society on the Report of the GOLD 2017 Global Strategy for the Diagnosis, Management, and Prevention of COPD

“…In patients with severe exacerbations, both treatment arms (LABA+LAMA vs ICS+LABA) provided comparable results. Most exacerbations during the followup were mild in the FLAME study [33]. Considering these findings, the evidence on patients with two or more exacerbations were not strong enough to refer certain treatment strategy.…”

CTS position statement: Pharmacotherapy in patients with COPD—An update

“…We suggest treatment with oral slow-release theophylline à to prevent AECOPD for patients on long-acting inhaled therapy (Grade 2B). 19 Although recent evidence supports the benefit of inhaled LAMA plus LABA dual therapy in preventing AECOPD 130 compared to a combination of ICS/LABA, further prospective comparisons are necessary, particularly in patient subgroups with 2 or more exacerbations per year or those with very severe airflow obstruction. These new data would suggest that for COPD patients who don't have concomitant asthma, step up from LAMA or LABA monotherapy to a LAMA plus LABA dual therapy is preferred over step up to combination ICS/ LABA.…”

Individualized Care in COPD: Updated Guidelines from Revised GOLD 2017 Report

“…Unlike asthma, there is no association between use of this class and increased mortality in COPD [30][31][32][33][34][35][36][37].…”