Triple Versus Dual Combination Therapy in Chronic Obstructive Pulmonary Disease in Asian Countries: Analysis of the IMPACT Trial

Overview

Journal Pulm Ther

Publisher Springer

Date 2020 Nov 17

PMID 33201438

Citations 5

Authors

David M G Halpin

Gerard J Criner

Mark T Dransfield

MeiLan K Han

Benjamin Hartley

Catherine Harvey

C Elaine Jones

Motokazu Kato

Peter Lange

Sally Lettis

David A Lomas

Fernando J Martinez

Neil Martin

Dave Singh

Robert Wise

Jinping Zheng

David A Lipson

Affiliations

Soon will be listed here.

Abstract

Introduction: In the IMPACT trial, single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) reduced moderate/severe exacerbation rates versus FF/VI or UMEC/VI dual therapy in patients with chronic obstructive pulmonary disease (COPD); however, pneumonia incidence was higher in FF-containing arms. As COPD is a growing problem in Asia, we compared the efficacy and safety of FF/UMEC/VI in Asia versus non-Asia regions.

Methods: IMPACT was a double-blind, 52-week trial in symptomatic COPD patients with ≥ 1 moderate/severe exacerbation in the prior year. This pre-specified analysis evaluated the annual rate of moderate/severe exacerbations, change from baseline in trough forced expiratory volume in 1 s, and St George's Respiratory Questionnaire total score, mortality, and safety (including pneumonia) in Asia versus non-Asia regions.

Results: The intent-to-treat population comprised 10,355 patients (Asia n = 1644 [16%]). Rate ratios (95% confidence intervals) for moderate/severe exacerbations with FF/UMEC/VI were 0.89 (0.76-1.05) versus FF/VI and 0.86 (0.71-1.04) versus UMEC/VI in Asia, and 0.84 (0.79-0.90) and 0.74 (0.68-0.80) in non-Asia. Efficacy of FF/UMEC/VI on other endpoints was similar in both regions. There was an increased incidence of investigator-reported pneumonia in patients in Asia (FF/UMEC/VI: 13%; FF/VI: 14%; UMEC/VI: 6%) compared with non-Asia (FF/UMEC/VI: 6%; FF/VI: 5%; UMEC/VI: 4%). The increased risk of pneumonia in patients in Asia was most marked in patients with lower body mass index, lower lung function, and taking inhaled corticosteroids. In post hoc analysis of adjudicated on-treatment all-cause mortality, probabilities of death were numerically lower in both regions with FF/UMEC/VI (Asia: 1.16%; non-Asia: 1.35%) and FF/VI (Asia: 1.77%; non-Asia: 1.21%) versus UMEC/VI (Asia: 1.91%; non-Asia: 2.23%).

Conclusions: FF/UMEC/VI provides similar benefits in COPD patients in Asia and non-Asia regions. Clinical benefits of treatment, including reduction in mortality risk, should be weighed against risk of pneumonia, taking account of all known risk factors.

Trial Registration: ClinicalTrials.gov identification, NCT02164513.

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