Exacerbation heterogeneity in COPD: subgroup analyses from the FLAME study

Background: The FLAME study compared once-daily indacaterol/glycopyrronium (IND/GLY) 110/50 mu g with twice-daily salmeterol/fluticasone (SFC) 50/500 mu g in symptomatic patients with moderate to very severe COPD and a history of exacerbations in the previous year. Methods: This prespecified and post hoc subgroup analysis evaluated treatment efficacy on 1) moderate/severe exacerbations according to prior exacerbation history and treatment, and 2) types of exacerbations according to health care resource utilization (HCRU) during 1-year follow-up. Results: IND/GLY reduced the rate of moderate/severe exacerbations versus SFC in patients with a history of 1 exacerbation (rate ratio [RR]: 0.83, 95% CI: 0.75-0.93), >= 2 exacerbations (RR: 0.85, 95% CI: 0.70-1.03) and >= 2 exacerbations or >= 1 hospitalization in the previous year (RR: 0.86, 95% CI: 0.74-1.00). Prolonged time-to-first exacerbation was observed in all the groups according to exacerbation history. Moderate/severe exacerbations decreased with IND/GLY versus SFC, independent of previous treatment. IND/GLY significantly reduced rates of moderate/severe exacerbations treated with antibiotics (RR: 0.79, 95% CI: 0.67-0.93) and systemic corticosteroids and antibiotics (RR: 0.80, 95% CI: 0.70-0.91); rates of exacerbations treated with systemic corticosteroids alone were comparable (RR: 0.99, 95% CI: 0.80-1.22). Conclusion: Overall, IND/GLY demonstrated consistent beneficial effects versus SFC on moderate/severe exacerbations, independent of prior exacerbation history or treatment. The efficacy of IND/GLY on exacerbation prevention was superior to SFC for exacerbations treated with antibiotics with/without systemic corticosteroids and was similar for exacerbations treated with systemic corticosteroids alone.