Introduction: One of the major goals of COPD treatment is to reduce the severity and frequency of exacerbations.1 Patients categorized into Global Initiative for Chronic Obstructive Lung Disease (GOLD) Group D have severe-to-very severe airflow limitation, and/or exacerbations, and significant symptoms.1 The GOLD strategy recommends a LABA/ICS or/and a LAMA as the first choice of treatment for Group D patients.1 FLAME was the first study that demonstrated the superiority of indacaterol/glycopyrronium (110/50 µg, once daily), a LABA/LAMA combination, in reducing exacerbations, improving lung function, and health status versus salmeterol/fluticasone, a LABA/ICS combination, in moderate-to-very severe COPD patients with a history of exacerbations.2 Here, we present data comparing the effect of indacaterol/glycopyrronium versus salmeterol/fluticasone on the rate and risk of moderate or severe exacerbations in a subset of GOLD Group D patients who had a history of ≥2 exacerbations or 1 hospitalization for exacerbation from the FLAME study.
Methods: FLAME was a 52-week, randomized, double-blind, double-dummy, parallel-group study. Patients with moderate-to-very severe COPD, post-bronchodilator forced expiratory volume in the 1 second ≥25% to <60% predicted normal, and a history of ≥1 exacerbation in the previous year were randomized (1:1) to receive either indacaterol/glycopyrronium (110/50 µg) once daily or salmeterol/fluticasone (50/500 µg) twice daily. The rate and time to moderate or severe exacerbations were analyzed in the subset of GOLD Group D patients with a history of ≥2 exacerbations or 1 hospitalization.
Results: Of the 3362 patients randomized, 2514 were categorized as GOLD Group D. The randomized patients had a mean post-bronchodilator FEV1 of 44.1% of the predicted normal value; 56.3% patients were on ICS at screening. Indacaterol/glycopyrronium demonstrated superior efficacy over salmeterol/fluticasone in reducing the rate of moderate or severe exacerbations (rate ratio, 0.86). Indacaterol/glycopyrronium delayed the time-to-first moderate or severe exacerbation compared with salmeterol/fluticasone (median days: 291 versus 215). The patients treated with indacaterol/glycopyrronium had a 19% lower risk of a moderate or severe exacerbation compared with salmeterol/fluticasone.
Conclusions: Indacaterol/glycopyrronium was superior to salmeterol/fluticasone in reducing the rate and risk of moderate or severe exacerbations in a subset of GOLD Group D patients who had a history of ≥2 exacerbations or 1 hospitalization for exacerbation. Our results confirm the use of indacaterol/glycopyrronium as a preferred treatment option for COPD patients at high risk of exacerbations.