Impact of triple therapy on mortality in COPD

Thibaud Soumagne; Maeva Zysman; Dilek Karadogan; Lies Lahousse; Alexander G. Mathioudakis

doi:10.1183/20734735.0260-2022

Tables

TABLE 1

Main characteristics of the IMPACT and ETHOS trials

Study (study period)	Inclusion/exclusion criteria			Treatment		Included patients	Characteristics of patients at inclusion
Study (study period)	Age and symptoms	FEV₁ and exacerbation history^#	History of asthma/ eosinophils	ICS use before inclusion	Treatment arms	Included patients	Mean age, years	Men (%)	Mean blood Eosinophils	Bronchodilator reversibility
IMPACT (2014–2017)	Age ≥40 years CAT ≥10	FEV₁ <50% and ≥1 moderate-to-severe exacerbation OR 50%<FEV₁<80% and ≥1 severe exacerbation or ≥2 moderate exacerbations	Prior (but not current) history of asthma allowed No restriction regarding blood eosinophils	70%	Randomisation 2:2:1 ratio: 1) ICS (FF)+LAMA (UMEC)+LABA (VI) (triple therapy); 2) ICS (FF)+LABA (VI); 3) LAMA (UMEC)+LABA (VI)	10 355	65	66%	170 cells per mm³	18%
ETHOS (2015–2019)	Age 40–80 years CAT ≥10	FEV₁ <50% and ≥1 moderate-to-severe exacerbation OR 50%<FEV₁<65% and ≥1 severe exacerbation or ≥2 moderate exacerbation	Prior (but not current) history of asthma allowed No restriction regarding blood eosinophils	80%	Randomisation 1:1:1:1 ratio: 1) ICS (BUD 320 µg)+LABA (FOR)+LAMA (GLY) (triple therapy, high-dose ICS) 2) ICS (BUD 160 µg)+LABA (FOR)+LAMA (GLY) (triple therapy, low-dose ICS) 3) ICS (BUD 320 µg)+LABA (FOR) 4) LAMA (GLY)+LABA (FOR)	8588	65	60%	167 cells per mm³	31%

FEV₁: forced expiratory volume in 1 s; CAT: COPD Assessment Test; ICS: inhaled corticosteroid; FF: fluticasone furoate; LAMA: long-acting muscarinic antagonist; UMEC: umeclidinium; LABA: long-acting β₂-agonist; VI: vilanterol; BUD: budesonide; GLY: glycopyrrolate; FOR: formoterol. ^#: exacerbation history in the past 12 months.

TABLE 2

Main outcomes of the IMPACT and ETHOS trials

Study	Primary outcome: rate of moderate/severe exacerbations per year	Secondary/exploratory outcomes
Study		Mean SGRQ	Lung function	Mortality
IMPACT	• 0.91 with triple therapy	Mean change from baseline in SGRQ:	Mean change from baseline in FEV₁:	• 50 (1.2%) deaths in the FF/UMEC/VI arm
	• 1.07 with FF/VI (RR with triple therapy of 0.85 (95% CI 0.80–0.90); p<0.001)	• −1.8 (−2.4 to −1.1; p <0.001) with triple therapy compared with FF/VI	• +97 mL (85–109); p<0.001 with triple therapy compared with FF/VI	• 49 (1.2%) in the FF/VI arm (no difference with FF/UMEC/VI)
	• 1.21 with UMEC/VI (RR with triple therapy of 0.75 (95% CI 0.70–0.81); p<0.001)	• −1.8 (−2.6 to −1.0; p <0.001) with triple therapy compared with UMEC/VI	• +54 mL (39–69); p<0.001 with triple therapy compared with UMEC/VI	• 39 (1.9%) in the UMEC/VI arm (HR of 0.58 (95% CI 0.38–0.88), p=0.011, between FF/UMEC/VI and UMEC/VI)
ETHOS	• 1.08 with high-dose triple-therapy	Mean change from baseline in SGRQ:	Least square means change from baseline in FEV₁:	• 28 (1.3%) deaths in the high-dose triple therapy arm
	• 1.07 with low-dose triple-therapy	• −1.88 (−2.84 to −0.91) with high-dose triple therapy compared with GLY/FOR	• +35 mL (12–57); p=0.003 with triple therapy compared with GLY/FOR	• 39 (1.8%) in the low-dose triple therapy arm (no difference with high-dose triple therapy arm)
	• 1.42 with GLY/FOR (RR with high-dose triple therapy of 0.76 (95% CI 0.69–0.83); p<0.001)	• −1.47 (−2.43 to −0.51) with high-dose triple therapy compared with BUD/FOR	• +76 mL (54–99); p<0.0001 with triple therapy compared with GLY/FOR	• 49 (2.3%) in the GLY/FOR arm (HR of 0.51 (95% CI 0.33–0.80), p=0.004, between triple therapy and GLY/FOR)
	• 1.24 with BUD/FOR (RR with high-dose triple therapy of 0.87 (95% CI 0.79–0.95); p=0.003)			• 34 (1.6%) in the BUD/FOR arm (HR of 0.72 (95% CI 0.44–1.16), p=0.17, between triple therapy and BUD/FOR)

SGRQ: St George's Respiratory Questionnaire; FEV₁: forced expiratory volume in 1 s; FF: fluticasone furoate; UMEC: umeclidinium; VI: vilanterol; RR: rate ratio; HR: hazard ratio; BUD: budesonide; GLY: glycopyrrolate; FOR: formoterol.