The IMPACT Study - Single Inhaler Triple Therapy (FF/UMEC/VI) Versus FF/VI And UMEC/VI In Patients With COPD: Efficacy And Safety In A Japanese Population

• Published in: International journal of chronic obstructive pulmonary disease Vol. 14; pp. 2849 - 2861
• Main Authors: Kato, Motokazu, Tomii, Keisuke, Hashimoto, Kenichi, Nezu, Yasuko, Ishii, Takeo, Jones, C Elaine, Kilbride, Sally, Gross, Annette S, Clifton, Christine S, Lipson, David A
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2019; Dove Medical Press Ltd; Dove; Dove Medical Press
• Subjects: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists - administration & dosage; Adrenergic beta-2 Receptor Agonists - adverse effects; Aged; Analysis; Androstadienes - administration & dosage; Androstadienes - adverse effects; Asthma; Benzyl Alcohols - administration & dosage; Benzyl Alcohols - adverse effects; Bronchodilator Agents - administration & dosage; Bronchodilator Agents - adverse effects; Chlorobenzenes - administration & dosage; Chlorobenzenes - adverse effects; Chronic obstructive lung disease; Chronic obstructive pulmonary disease; copd exacerbation; Demographics; Disease Progression; Double-Blind Method; Drug Combinations; Drug therapy; Dyspnea; Female; fluticasone furoate; Forced Expiratory Volume; Generalized linear models; Health Status; Humans; Inhalers; Japan; Lung - drug effects; Lung - physiopathology; Male; Middle Aged; Muscarinic Antagonists - administration & dosage; Muscarinic Antagonists - adverse effects; Nebulizers and Vaporizers; Original Research; Patients; Pneumonia; Population; Pulmonary Disease, Chronic Obstructive - diagnosis; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - physiopathology; Quinuclidines - administration & dosage; Quinuclidines - adverse effects; Recovery of Function; Respiratory system agents; Time Factors; Treatment Outcome; triple therapy; umeclidinium; Vilanterol; Japan; Asia; fluticasone furoate; COPD exacerbation; triple therapy; umeclidinium; Japan; vilanterol
• ISSN: 1178-2005; 1176-9106; 1178-2005
• DOI: 10.2147/COPD.S226601

The Informing the Pathway of COPD Treatment (IMPACT) study demonstrated that single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) reduces moderate/severe exacerbation rates and improves lung function and health status versus FF/VI or UMEC/VI dual therapy in patients with symptomatic COPD and a history of exacerbations. This analysis evaluated the efficacy and safety of FF/UMEC/VI in patients enrolled in Japan. IMPACT was a 52-week, randomized, double-blind, multicenter study comparing FF/UMEC/VI 100/62.5/25 µg with FF/VI 100/25 µg or UMEC/VI 62.5/25 µg in patients ≥40 years with symptomatic COPD and ≥1 moderate/severe exacerbation in the previous year. Endpoints included annual rate of on-treatment moderate/severe exacerbations (primary endpoint), time-to-first on-treatment moderate/severe exacerbation and change from baseline at Week 52 in trough FEV , post-bronchodilator FEV , St. George's Respiratory Questionnaire, and COPD Assessment Test score. Safety was also assessed. The Japan subgroup accounted for only 4% (378/10,355) of the overall IMPACT intent-to-treat (ITT) population. In the Japan subgroup, FF/UMEC/VI reduced the annual rate of on-treatment moderate/severe exacerbations by 15% (95% CI: -20, 40) versus FF/VI (compared with 15% [10, 20] in the ITT) and 36% (95% CI: 6, 57) versus UMEC/VI (compared with 25% [19, 30] in the ITT). FF/UMEC/VI reduced moderate/severe exacerbation risk (time-to-first), improved lung function and health status at Week 52 versus both dual therapies. These results were in the same direction and of a generally similar magnitude to those seen in the overall ITT population. No new safety signals were identified in the Japan subgroup compared with the ITT population. Pneumonia incidence was higher with FF/UMEC/VI and FF/VI versus UMEC/VI. These results highlight the favorable benefit-risk profile of FF/UMEC/VI single-inhaler triple therapy compared with FF/VI or UMEC/VI dual therapy in patients in Japan with symptomatic COPD and ≥1 exacerbation in the prior year.