Once-daily single-inhaler versus twice-daily multiple-inhaler triple therapy in patients with COPD: lung function and health status results from two replicate randomized controlled trials

Respiratory Research

卷:21

David Bernstein¹  Chang-Qing Zhu²  David A. Lipson²  Thomas C. Corbridge²  Catherine Harvey²  Chris Compton²  Marjorie Stiegler²  Morrys C. Kaisermann²  Neil Martin²  Kelly Dorais²  Nicola Brown²  Gary T. Ferguson³  Charles Fogarty⁴  Frank Sciurba⁵ 

[1] Bernstein Clinical Research Center and Division of Immunology, Allergy and Rheumatology, University of Cincinnati College of Medicine;

[2] GlaxoSmithKline;

[3] Pulmonary Research Institute of Southeast Michigan;

[4] Spartanburg Medical Research;

[5] University of Pittsburgh Medical Center;

关键词: Triple therapy;    COPD;    Lung function;    Symptoms;    Long-acting β2-agonist (LABA);    Long-acting muscarinic antagonist (LAMA);   

DOI  :  10.1186/s12931-020-01360-w

来源: DOAJ

【 摘 要 】

Abstract Background The comparative efficacy of inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2-agonist (ICS/LAMA/LABA) triple therapy administered via single or multiple inhalers in patients with chronic obstructive pulmonary disease (COPD) has not been evaluated comprehensively. We conducted two replicate trials comparing single- with multiple-inhaler ICS/LAMA/LABA combination in COPD. Methods 207608 and 207609 were Phase IV, 12-week, randomized, double-blind, triple-dummy non-inferiority trials comparing once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 μg via Ellipta inhaler, with twice-daily budesonide/formoterol (BUD/FOR) 400/12 μg via metered-dose inhaler plus once-daily tiotropium (TIO) 18 μg via HandiHaler. Patients had symptomatic COPD and forced expiratory volume in 1 s (FEV1) < 50% predicted, or FEV1 < 80% predicted and ≥ 2 moderate or 1 severe exacerbations in the prior year. The primary endpoint in both trials was weighted mean change from baseline (wmCFB) in 0–24-h FEV1 at Week 12. Secondary endpoints included CFB in trough FEV1 at Day 84 and 85. Other endpoints included serial FEV1 and health status outcomes at Week 12. Safety was evaluated descriptively. Results The modified per-protocol population included 720 and 711 patients in studies 207608 and 207609 (intent-to-treat population: 728 and 732). FF/UMEC/VI was non-inferior to BUD/FOR+TIO for wmCFB in 0–24-h FEV1 at Week 12 (Study 207608 treatment difference [95% confidence interval]: 15 mL [− 13, 43]; Study 207609: 11 mL [− 20, 41]). FF/UMEC/VI improved trough FEV1 CFB versus BUD/FOR+TIO at Day 84 and 85 (Day 85 treatment difference: Study 207608: 38 mL [10, 66]; Study 207609: 51 mL [21, 82]) and FEV1 at 12 and 24 h post-morning dose at Week 12 in both studies. No treatment differences were seen in health status outcomes. Safety profiles were similar between treatments; pneumonia occurred in 7 (< 1%) patients with FF/UMEC/VI and 9 (1%) patients with BUD/FOR+TIO, across both studies. Conclusions FF/UMEC/VI was non-inferior to BUD/FOR+TIO for wmCFB in 0–24-h FEV1 at Week 12 in patients with COPD. Greater improvements in trough and serial FEV1 measurements at Week 12 with FF/UMEC/VI versus BUD/FOR+TIO, together with similar health status improvements and safety outcomes including the incidence of pneumonia, suggest that once-daily single-inhaler FF/UMEC/VI triple therapy is a viable option for patients looking to simplify their treatment regimen. Trial registration GSK (207608/207609; NCT03478683 / NCT03478696 ).

【 授权许可】

Unknown