| الوصف: |
Motokazu Kato,1 Keisuke Tomii,2 Kenichi Hashimoto,3 Yasuko Nezu,3 Takeo Ishii,4 C Elaine Jones,5 Sally Kilbride,6 Annette S Gross,7 Christine S Clifton,7 David A Lipson8,9 1Chest Disease Clinical and Research Institute, Kishiwada City Hospital, Kishiwada, Japan; 2Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan; 3Evidence Generation Department, GlaxoSmithKline K.K., Tokyo, Japan; 4MA Respiratory Department, GlaxoSmithKline K.K., Tokyo, Japan; 5Development, R&D, GlaxoSmithKline, Research Triangle Park, NC, USA; 6Biostatistics, GlaxoSmithKline, Uxbridge, Middlesex, UK; 7Clinical Pharmacology Modelling & Simulation, GlaxoSmithKline R&D, Sydney, Australia; 8Clinical Sciences, GlaxoSmithKline, Collegeville, PA, USA; 9Pulmonary, Allergy and Critical Care Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USACorrespondence: Yasuko NezuEvidence Generation Department, Respiratory Medical Affairs & Development GlaxoSmithKline K.K., Akasaka Intercity AIR 1-8-1 Akasaka, Minato-Ku, Tokyo 107-0052, JapanTel +81 3 4231 5064Fax +81 3 4231 5994Email yasuko.2.nezu@gsk.comPurpose: 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.Patients and methods: 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 FEV1, post-bronchodilator FEV1, St. George’s Respiratory Questionnaire, and COPD Assessment Test score. Safety was also assessed.Results: 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.Conclusion: 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.Keywords: triple therapy, fluticasone furoate, Japan, umeclidinium, vilanterol, COPD exacerbation |
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