PT  - JOURNAL ARTICLE
AU  - Halpin, David M.G.
AU  - Dransfield, Mark T.
AU  - Han, MeiLan K.
AU  - Jones, C. Elaine
AU  - Kilbride, Sally
AU  - Lange, Peter
AU  - Lipson, David A.
AU  - Lomas, David A.
AU  - Martinez, Fernando J.
AU  - Pascoe, Steve
AU  - Singh, Dave
AU  - Wise, Robert
AU  - Criner, Gerard J.
TI  - The effect of exacerbation history on outcomes in the IMPACT trial
AID  - 10.1183/13993003.01921-2019
DP  - 2020 May 01
TA  - European Respiratory Journal
PG  - 1901921
VI  - 55
IP  - 5
4099  - http://erj.ersjournals.com/content/55/5/1901921.short
4100  - http://erj.ersjournals.com/content/55/5/1901921.full
SO  - Eur Respir J2020 May 01; 55
AB  - IMPACT, a 52-week, randomised, double-blind trial, assessed the efficacy and safety of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus FF/VI or UMEC/VI in patients with symptomatic COPD and a history of exacerbations.Subgroup analyses assessed whether the efficacy of FF/UMEC/VI versus FF/VI or UMEC/VI and UMEC/VI versus FF/VI varies according to prior exacerbation history, and the combined effects of exacerbation history and blood eosinophil counts. Three subgroups were defined: single moderate (1 moderate/no severe; n=3056 (30%)), frequent moderate (≥2 moderate/no severe; n=4628 (45%)) and severe (≥1 severe/any moderate; n=2671 (26%)). End-points included annual on-treatment moderate/severe exacerbation rate (pre-specified), lung function and health status (both post-hoc).Moderate/severe exacerbation rates (reduction % (95% CI)) were reduced in the FF/UMEC/VI group versus FF/VI (single moderate 20% (10–29), frequent moderate 11% (2–19), severe 17% (7–26)) and versus UMEC/VI (single moderate 18% (5–29), frequent moderate 29% (21–37), severe 26% (14–35)). Moderate/severe exacerbation rates were reduced in the FF/VI group versus UMEC/VI in the frequent moderate subgroup; a numerical reduction was observed in the severe subgroup (single moderate 2% (−12–18), frequent moderate 21% (11–29), severe 11% (−3–22)). Moderate/severe exacerbation rates were lower in the FF/VI group compared with UMEC/VI in patients with higher eosinophil counts. FF/UMEC/VI improved lung function and health status versus both dual therapies irrespective of exacerbation subgroup. UMEC/VI improved lung function versus FF/VI in all subgroups.Triple therapy was more effective than dual regardless of exacerbation history, consistent with results in the intent-to-treat population. Comparisons between dual therapies were influenced by prior exacerbation history and eosinophil counts.FF/UMEC/VI shows benefits vs FF/VI and UMEC/VI across multiple endpoints irrespective of exacerbation history. Exacerbation history and eosinophils influenced the comparison between UMEC/VI and FF/VI, and eosinophils that between FF/UMEC/VI and UMEC/VI. http://bit.ly/2SHu2ey