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Benefit/Risk Profile of Single-Inhaler Triple Therapy in COPD

Authors Bourbeau J, Bafadhel M, Barnes NC, Compton C, Di Boscio V, Lipson DA, Jones PW, Martin N, Weiss G, Halpin DMG

Received 13 November 2020

Accepted for publication 7 February 2021

Published 1 March 2021 Volume 2021:16 Pages 499—517


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Richard Russell

Jean Bourbeau,1 Mona Bafadhel,2 Neil C Barnes,3,4 Chris Compton,3 Valentina Di Boscio,3 David A Lipson,5,6 Paul W Jones,3,7 Neil Martin,3,8 Gudrun Weiss,3 David MG Halpin9

1Respiratory Epidemiology and Clinical Research Unit, Department of Medicine, McGill University and Research Institute of the McGill University Health Centre, Montreal, QC, Canada; 2Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, UK; 3Respiratory Therapy Area, GlaxoSmithKline, Brentford, Middlesex, UK; 4William Harvey Institute, Bart’s and the London School of Medicine and Dentistry, London, UK; 5Clinical Sciences, GlaxoSmithKline, Collegeville, PA, USA; 6Pulmonary, Allergy and Critical Care Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 7Institute of Infection and Immunity, St George’s, University of London, London, UK; 8University of Leicester, Leicester, UK; 9University of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, UK

Correspondence: Jean Bourbeau
McGill University Health Centre (MUHC), 1001 Decarie Boulevard, Montreal, QC, H4A 3J1, Canada
Tel +1 514 934-1934
Fax +1 514 934-8577
Email jean.bour[email protected]

Abstract: Chronic obstructive pulmonary disease (COPD) is associated with major healthcare and socioeconomic burdens. International consortia recommend a personalized approach to treatment and management that aims to reduce both symptom burden and the risk of exacerbations. Recent clinical trials have investigated single-inhaler triple therapy (SITT) with a long-acting muscarinic antagonist (LAMA), long-acting β2-agonist (LABA), and inhaled corticosteroid (ICS) for patients with symptomatic COPD. Here, we review evidence from randomized controlled trials showing the benefits of SITT and weigh these against the reported risk of pneumonia with ICS use. We highlight the challenges associated with cross-trial comparisons of benefit/risk, discuss blood eosinophils as a marker of ICS responsiveness, and summarize current treatment recommendations and the position of SITT in the management of COPD, including potential advantages in terms of improving patient adherence. Evidence from trials of SITT versus dual therapies in symptomatic patients with moderate to very severe airflow limitation and increased risk of exacerbations shows benefits in lung function and patient-reported outcomes. Moreover, the key benefits reported with SITT are significant reductions in exacerbations and hospitalizations, with data also suggesting reduced all-cause mortality. These benefits outweigh the ICS-class effect of higher incidence of study-reported pneumonia compared with LAMA/LABA. Important differences in trial design, baseline population characteristics, such as exacerbation history, and assessment of outcomes, have significant implications for interpreting data from cross-trial comparisons. Current understanding interprets the blood eosinophil count as a continuum that can help predict response to ICS and has utility alongside other clinical factors to aid treatment decision-making. We conclude that treatment decisions in COPD should be guided by an approach that considers benefit versus risk, with early optimization of treatment essential for maximizing long-term benefits and patient outcomes.

Keywords: all-cause mortality, exacerbations, hospitalizations, ICS, LABA, LAMA

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