부산대학교 도서관

Results from FULFIL have shown statistically significant improvements in lung function and health-related quality of life, and a reduction in exacerbation rates with once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100 µg/62.5 µg/25 µg administered using a single ELLIPTA®inhaler compared with twice-daily budesonide/formoterol (BUD/FOR) 400 µg/12 µg using the Turbuhaler®in patients with symptomatic COPD at risk of exacerbations. The safety profile of FF/UMEC/VI reflected that of the components (Lipson, et al. Am J Respir Crit Care Med. 2017). Herein we present post-hocsubgroup analyses of exacerbation rates by prior COPD medication class, disease severity and exacerbation history during FULFIL. In the intent-to-treat (ITT; 24 weeks) population, the mean annual exacerbation rate, FF/UMEC/VI versus BUD/FOR ratios and annual exacerbation rates reductions were calculated for subgroups: by prior COPD medication class, inhaled corticosteroid (ICS) +long acting beta agonists (LABA); BUD/FOR; ICS +LABA + long-acting muscarinic antagonists (LAMA); LAMA; tiotropium; LAMA +LABA; by disease severity, forced expiratory volume in 1 s (FEV1) <50% predicted, no moderate/severe exacerbation; FEV1<50%,≥1 moderate/severe exacerbation; FEV1≥50–≤80%,≥2 moderate or ≥1 severe exacerbations; and by exacerbation history, 0/1 moderate exacerbations;≥2 moderate exacerbations;≥1 severe exacerbation. Up to Week 24 in the ITT population, FF/UMEC/VI versus BUD/FOR improved the mean annual exacerbation rate (range, 63%–24%) in all prior medication subgroups, except LAMA +LABA (annual exacerbation rate reduction, −44%) and improved mean annual exacerbation rates in all disease severity (range, 45%–27%) and exacerbation prior history (range, 57%–27%) subgroups (Table). Statistical significance of the FF/UMEC/VI:BUD/FOR ratio was observed for the subgroups: prior medication class ICS +LABA (0.37; 95% confidence interval [CI] 0.20–0.71; p=0.003) and ICS +LAMA + LABA (0.53; 95% CI 0.33–0.87; p=0.012); disease severity FEV1<50% and≥1 moderate/severe exacerbation (0.55; 0.34–0.89; p=0.015); exacerbation history 0/1 prior moderate exacerbation (0.62; 0.44 0.87; p=0.005) and ≥1 prior severe exacerbation (0.43; 0.22 0.86; p=0.017) (Table). Improvements in mean annual exacerbation rates with once-daily FF/UMEC/VI compared with twice-daily BUD/FOR were observed in all patients regardless of disease severity or exacerbation history and all prior COPD medication class subgroups except for LAMA +LABA.FundingGSK (NCT02345161; CTT116853)Please refer to page A260 for declarations of interest in relation to abstract P272.Abstract P272 Table 1Mean annual exacerbation rates by subgroup (ITT population; up to Week 24)SubgroupFF/UMEC/VI 100/62.5/25 µg (n=911)BUD/FOR400/12 µg (n=899)Reduction in annual exacerbation ratenratenrate%(95% CI)Prior medication ICS+LABA 266 0.10 258 0.27 63* (29–80) BUD+FOR 87 0.05 83 0.10 54 (−74–88) ICS+LABA+LAMA 256 0.28 254 0.53 47* (13–67) LAMA alone 79 0.12 79 0.23 49 (−42–81) TIO alone 65 0.15 67 0.20 24 (−125–74) LAMA+LABA 100 0.38 83 0.26 −44 (−194–29) Disease severity FEV1<50%, no moderate/severe exacerbations 311 0.22 315 0.33 33 (−4–57) FEV1<50%,≥1 moderate/severe exacerbation 299 0.22 290 0.41 45* (11–66) FEV1≥50–≤80%,≥2 moderate/≥1 severe exacerbations 296 0.22 289 0.30 27 (−21–56) Exacerbation history 0/1 moderate 599 0.23 609 0.37 38* (13–56) ≥2 moderate 308 0.01 283 0.02 27 (−20–55)≥1 severe 185 0.12 200 0.29 57* (14–78) *Statistically significant difference for FF/UMEC/VI:BUD/FOR ratio; CI, confidence interval; ICS, inhaled corticosteroid; ITT, intent-to-treat; LABA, long-acting beta agonists; LAMA, long-acting muscarinic antagonists; TIO, tiotropium.