Effect of Age on the Efficacy and Safety of Once-Daily Single-Inhaler Triple-Therapy Fluticasone Furoate/Umeclidinium/Vilanterol in Patients With COPD

Background In the Informing the Pathway of COPD Treatment (IMPACT) trial, single-inhaler triple-therapy fluticasone furoate (FF), umeclidinium (UMEC), and vilanterol (VI) reduced moderate/severe exacerbation rates vs FF/VI and UMEC/VI in patients with symptomatic COPD and a history of exacerbations, with a similar safety profile. Research Question Are trial outcomes with single-inhaler triple-therapy FF/UMEC/VI vs FF/VI and UMEC/VI affected by age in patients with symptomatic COPD and a history of exacerbations? Study Design and Methods IMPACT was a phase III, double-blind, 52-week trial. Patients ≥ 40 years of age with symptomatic COPD and ≥ 1 moderate/severe exacerbation in the previous year were randomly assigned 2:2:1 to FF/UMEC/VI 100/62.5/25 μg, FF/VI 100/25 μg, or UMEC/VI 62.5/25 μg. End points assessed by age included annual rate of moderate/severe exacerbations, change from baseline (CFB) in trough FEV1, proportion of St. George’s Respiratory Questionnaire (SGRQ) responders (≥ 4 units decrease from baseline in SGRQ total score), and safety. Results The intention-to-treat population comprised 10,355 patients; 4,724 (46%), 4,225 (41%), and 1,406 (14%) were ≤ 64, 65 to 74, and ≥ 75 years of age, respectively. FF/UMEC/VI reduced on-treatment moderate/severe exacerbation rates vs FF/VI (% reduction [95% CI]: ≤ 64 years, 8% [−1 to 16]; P = .070; 65-74 years, 22% [14-29]; P < .001; ≥ 75 years, 18% [3-31]; P = .021) and vs UMEC/VI (≤ 64 years, 16% [7-25]; P = .002; 65-74 years, 33% [25-41]; P < .001; ≥ 75 years, 24% [6-38]; P = .012), with greatest rate reduction seen in the 65 to 74 and ≥ 75 years subgroups. Post hoc analyses of CFB in trough FEV1 and proportion of SGRQ responders at week 52 were significantly greater with FF/UMEC/VI than with FF/VI or UMEC/VI in all subgroups. No new safety signals were identified. Interpretation FF/UMEC/VI reduced the rate of moderate/severe exacerbations and improved lung function and health status vs FF/VI and UMEC/VI irrespective of age for most end points, with a similar safety profile. Clinical Trial Registration ClinicalTrials.gov; No.: NCT02164513; URL: www.clinicaltrials.govCTT116855 In the Informing the Pathway of COPD Treatment (IMPACT) trial, single-inhaler triple-therapy fluticasone furoate (FF), umeclidinium (UMEC), and vilanterol (VI) reduced moderate/severe exacerbation rates vs FF/VI and UMEC/VI in patients with symptomatic COPD and a history of exacerbations, with a similar safety profile. Are trial outcomes with single-inhaler triple-therapy FF/UMEC/VI vs FF/VI and UMEC/VI affected by age in patients with symptomatic COPD and a history of exacerbations? IMPACT was a phase III, double-blind, 52-week trial. Patients ≥ 40 years of age with symptomatic COPD and ≥ 1 moderate/severe exacerbation in the previous year were randomly assigned 2:2:1 to FF/UMEC/VI 100/62.5/25 μg, FF/VI 100/25 μg, or UMEC/VI 62.5/25 μg. End points assessed by age included annual rate of moderate/severe exacerbations, change from baseline (CFB) in trough FEV1, proportion of St. George’s Respiratory Questionnaire (SGRQ) responders (≥ 4 units decrease from baseline in SGRQ total score), and safety. The intention-to-treat population comprised 10,355 patients; 4,724 (46%), 4,225 (41%), and 1,406 (14%) were ≤ 64, 65 to 74, and ≥ 75 years of age, respectively. FF/UMEC/VI reduced on-treatment moderate/severe exacerbation rates vs FF/VI (% reduction [95% CI]: ≤ 64 years, 8% [−1 to 16]; P = .070; 65-74 years, 22% [14-29]; P < .001; ≥ 75 years, 18% [3-31]; P = .021) and vs UMEC/VI (≤ 64 years, 16% [7-25]; P = .002; 65-74 years, 33% [25-41]; P < .001; ≥ 75 years, 24% [6-38]; P = .012), with greatest rate reduction seen in the 65 to 74 and ≥ 75 years subgroups. Post hoc analyses of CFB in trough FEV1 and proportion of SGRQ responders at week 52 were significantly greater with FF/UMEC/VI than with FF/VI or UMEC/VI in all subgroups. No new safety signals were identified. FF/UMEC/VI reduced the rate of moderate/severe exacerbations and improved lung function and health status vs FF/VI and UMEC/VI irrespective of age for most end points, with a similar safety profile. ClinicalTrials.gov; No.: NCT02164513; URL: www.clinicaltrials.govCTT116855