TY - JOUR
T1 - Risk of exacerbation and pneumonia with single-inhaler triple versus dual therapy in IMPACT
AU - Dransfield, Mark T.
AU - Crim, Courtney
AU - Criner, Gerard J.
AU - Day, Nicola C.
AU - Halpin, David M.G.
AU - Han, Mei Lan K.
AU - Elaine Jones, C.
AU - Kilbride, Sally
AU - LaFon, David
AU - Lipson, David A.
AU - Lomas, David A.
AU - Martin, Neil
AU - Martinez, Fernando J.
AU - Singh, Dave
AU - Wise, Robert A.
AU - Lange, Peter
N1 - Funding Information:
Supported by GlaxoSmithKline (study number CTT116855). The funders of the study had a role in the study design, data analysis, data interpretation, and writing of the report. Editorial support (in the form of assembling figures, collating author comments, and grammatical editing) was provided by Chrystelle Rasamison, at Fishawack Indicia Ltd., UK, and was funded by GlaxoSmithKline. D.S. is supported by the National Institute for Health Research Manchester Biomedical Research Centre.
Publisher Copyright:
Copyright © 2021 by the American Thoracic Society
PY - 2021/5
Y1 - 2021/5
N2 - Rationale: In the IMPACT (Informing the Pathway of COPD Treatment) trial, single-inhaler fluticasone furoate/umeclidinium/ vilanterol (FF/UMEC/VI) triple therapy reduced exacerbation risk versus FF/VI and UMEC/VI and mortality risk versus UMEC/VI. However, pneumonia incidence was higher in the inhaled corticosteroid (FF)–containing arms, raising questions about the relative benefit of exacerbation reduction compared with the increased risk of pneumonia. Objectives: Determine benefit–risk of the three treatments by evaluating time-to-first and rates of composite exacerbation or pneumonia outcomes. Methods: We evaluated time-to-first (prespecified) and rates (post hoc) of investigator-reported pneumonia, serious pneumonia leading to hospitalization or death, and the composite endpoints of 1) moderate (required antibiotics/corticosteroids)/ severe (hospitalized) exacerbation or pneumonia and 2) severe exacerbation or serious (hospitalized) pneumonia. Analyses were repeated for radiographically confirmed pneumonia (post hoc). Results: Moderate/severe exacerbations occurred in 47%, 49%, and 50% of patients randomized to FF/UMEC/VI, FF/VI and UMEC/VI, and pneumonias in 8%, 7%, and 5%, respectively. FF/UMEC/VI reduced the risk of combined moderate/severe exacerbation or pneumonia (time-to-first) versus FF/VI (hazard ratio, 0.87 [95% confidence interval (CI), 0.82–0.92]) and UMEC/VI (0.87 [0.81–0.94]), as well as the risk of combined severe exacerbation or serious pneumonia versus UMEC/VI (0.83 [0.72–0.96]). FF/UMEC/VI reduced the rate of combined moderate/severe exacerbation or pneumonia (rate ratio, 0.78 [0.72–0.84]) and combined severe exacerbation or serious pneumonia (rate ratio, 0.76 [0.65–0.89]) versus UMEC/VI. Results were similar for radiographically confirmed pneumonia endpoints. Conclusions: Despite higher incidence of pneumonia in FF-containing arms, these composite exacerbation/pneumonia outcomes support a favorable benefit–risk profile of FF/UMEC/VI versus FF/VI and UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease and a history of exacerbations.
AB - Rationale: In the IMPACT (Informing the Pathway of COPD Treatment) trial, single-inhaler fluticasone furoate/umeclidinium/ vilanterol (FF/UMEC/VI) triple therapy reduced exacerbation risk versus FF/VI and UMEC/VI and mortality risk versus UMEC/VI. However, pneumonia incidence was higher in the inhaled corticosteroid (FF)–containing arms, raising questions about the relative benefit of exacerbation reduction compared with the increased risk of pneumonia. Objectives: Determine benefit–risk of the three treatments by evaluating time-to-first and rates of composite exacerbation or pneumonia outcomes. Methods: We evaluated time-to-first (prespecified) and rates (post hoc) of investigator-reported pneumonia, serious pneumonia leading to hospitalization or death, and the composite endpoints of 1) moderate (required antibiotics/corticosteroids)/ severe (hospitalized) exacerbation or pneumonia and 2) severe exacerbation or serious (hospitalized) pneumonia. Analyses were repeated for radiographically confirmed pneumonia (post hoc). Results: Moderate/severe exacerbations occurred in 47%, 49%, and 50% of patients randomized to FF/UMEC/VI, FF/VI and UMEC/VI, and pneumonias in 8%, 7%, and 5%, respectively. FF/UMEC/VI reduced the risk of combined moderate/severe exacerbation or pneumonia (time-to-first) versus FF/VI (hazard ratio, 0.87 [95% confidence interval (CI), 0.82–0.92]) and UMEC/VI (0.87 [0.81–0.94]), as well as the risk of combined severe exacerbation or serious pneumonia versus UMEC/VI (0.83 [0.72–0.96]). FF/UMEC/VI reduced the rate of combined moderate/severe exacerbation or pneumonia (rate ratio, 0.78 [0.72–0.84]) and combined severe exacerbation or serious pneumonia (rate ratio, 0.76 [0.65–0.89]) versus UMEC/VI. Results were similar for radiographically confirmed pneumonia endpoints. Conclusions: Despite higher incidence of pneumonia in FF-containing arms, these composite exacerbation/pneumonia outcomes support a favorable benefit–risk profile of FF/UMEC/VI versus FF/VI and UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease and a history of exacerbations.
KW - Benefit–risk assessment
KW - Chronic obstructive pulmonary disease
KW - Corticosteroids
KW - Exacerbations
KW - Pneumonia
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U2 - 10.1513/AnnalsATS.202002-096OC
DO - 10.1513/AnnalsATS.202002-096OC
M3 - Article
C2 - 33108212
AN - SCOPUS:85102241334
SN - 2329-6933
VL - 18
SP - 788
EP - 798
JO - Annals of the American Thoracic Society
JF - Annals of the American Thoracic Society
IS - 5
ER -