Risk of Exacerbation and Pneumonia with Single-Inhaler Triple versus Dual Therapy in IMPACT

Mark T. Dransfield; Courtney Crim; Gerard J. Criner; Nicola C. Day; David M. G. Halpin; MeiLan K. Han; C. Elaine Jones; Sally Kilbride; David LaFon; David A. Lipson; David A. Lomas; Neil Martin; Fernando J. Martinez; Dave Singh; Robert A. Wise; Peter Lange

doi:10.1513/AnnalsATS.202002-096OC

Risk of Exacerbation and Pneumonia with Single-Inhaler Triple versus Dual Therapy in IMPACT

Mark T. Dransfield^*, Courtney Crim, Gerard J. Criner, Nicola C. Day, David M. G. Halpin, MeiLan K. Han, C. Elaine Jones, Sally Kilbride, David LaFon, David A. Lipson, David A. Lomas, Neil Martin, Fernando J. Martinez, Dave Singh, Robert A. Wise, Peter Lange

^*Corresponding author af dette arbejde

Afdeling for Epidemiologi

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

21 Citationer (Scopus)

22 Downloads (Pure)

Abstract

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 andUMEC/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.

Originalsprog	Engelsk
Tidsskrift	Annals of the American Thoracic Society
Vol/bind	18
Udgave nummer	5
Sider (fra-til)	788-798
Antal sider	11
ISSN	1546-3222
DOI	https://doi.org/10.1513/AnnalsATS.202002-096OC
Status	Udgivet - 2021

Adgang til dokumentet

10.1513/AnnalsATS.202002-096OCLicens: CC BY

Risk of Exacerbation and Pneumonia with Single-Inhaler Triple versus Dual Therapy in IMPACTForlagets udgivne version, 862 KBLicens: CC BY

Citationsformater

Dransfield, M. T., Crim, C., Criner, G. J., Day, N. C., Halpin, D. M. G., Han, M. K., Jones, C. E., Kilbride, S., LaFon, D., Lipson, D. A., Lomas, D. A., Martin, N., Martinez, F. J., Singh, D., Wise, R. A., & Lange, P. (2021). Risk of Exacerbation and Pneumonia with Single-Inhaler Triple versus Dual Therapy in IMPACT. Annals of the American Thoracic Society, 18(5), 788-798. https://doi.org/10.1513/AnnalsATS.202002-096OC

Risk of Exacerbation and Pneumonia with Single-Inhaler Triple versus Dual Therapy in IMPACT. / Dransfield, Mark T.; Crim, Courtney; Criner, Gerard J.; Day, Nicola C.; Halpin, David M. G.; Han, MeiLan K.; Jones, C. Elaine; Kilbride, Sally; LaFon, David; Lipson, David A.; Lomas, David A.; Martin, Neil; Martinez, Fernando J.; Singh, Dave; Wise, Robert A.; Lange, Peter.

I: Annals of the American Thoracic Society, Bind 18, Nr. 5, 2021, s. 788-798.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Dransfield, MT, Crim, C, Criner, GJ, Day, NC, Halpin, DMG, Han, MK, Jones, CE, Kilbride, S, LaFon, D, Lipson, DA, Lomas, DA, Martin, N, Martinez, FJ, Singh, D, Wise, RA & Lange, P 2021, 'Risk of Exacerbation and Pneumonia with Single-Inhaler Triple versus Dual Therapy in IMPACT', Annals of the American Thoracic Society, bind 18, nr. 5, s. 788-798. https://doi.org/10.1513/AnnalsATS.202002-096OC

Dransfield, Mark T. ; Crim, Courtney ; Criner, Gerard J. ; Day, Nicola C. ; Halpin, David M. G. ; Han, MeiLan K. ; Jones, C. Elaine ; Kilbride, Sally ; LaFon, David ; Lipson, David A. ; Lomas, David A. ; Martin, Neil ; Martinez, Fernando J. ; Singh, Dave ; Wise, Robert A. ; Lange, Peter. / Risk of Exacerbation and Pneumonia with Single-Inhaler Triple versus Dual Therapy in IMPACT. I: Annals of the American Thoracic Society. 2021 ; Bind 18, Nr. 5. s. 788-798.

@article{e7249d0293594fc8aab7cb3bbeef4130,

title = "Risk of Exacerbation and Pneumonia with Single-Inhaler Triple versus Dual Therapy in IMPACT",

abstract = "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 andUMEC/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.",

keywords = "chronic obstructive pulmonary disease, benefit-risk assessment, pneumonia, exacerbations, corticosteroids, OBSTRUCTIVE PULMONARY-DISEASE, COMMUNITY-ACQUIRED PNEUMONIA, FLUTICASONE FUROATE, HOSPITAL MORTALITY, COPD PATIENTS, DECAF SCORE, VILANTEROL",

author = "Dransfield, {Mark T.} and Courtney Crim and Criner, {Gerard J.} and Day, {Nicola C.} and Halpin, {David M. G.} and Han, {MeiLan K.} and Jones, {C. Elaine} and Sally Kilbride and David LaFon and Lipson, {David A.} and Lomas, {David A.} and Neil Martin and Martinez, {Fernando J.} and Dave Singh and Wise, {Robert A.} and Peter Lange",

year = "2021",

doi = "10.1513/AnnalsATS.202002-096OC",

language = "English",

volume = "18",

pages = "788--798",

journal = "Annals of the American Thoracic Society",

issn = "2325-6621",

publisher = "American Thoracic Society",

number = "5",

}

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, MeiLan K.

AU - Jones, C. Elaine

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

PY - 2021

Y1 - 2021

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 andUMEC/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 andUMEC/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 - chronic obstructive pulmonary disease

KW - benefit-risk assessment

KW - pneumonia

KW - exacerbations

KW - corticosteroids

KW - OBSTRUCTIVE PULMONARY-DISEASE

KW - COMMUNITY-ACQUIRED PNEUMONIA

KW - FLUTICASONE FUROATE

KW - HOSPITAL MORTALITY

KW - COPD PATIENTS

KW - DECAF SCORE

KW - VILANTEROL

U2 - 10.1513/AnnalsATS.202002-096OC

DO - 10.1513/AnnalsATS.202002-096OC

M3 - Journal article

C2 - 33108212

VL - 18

SP - 788

EP - 798

JO - Annals of the American Thoracic Society

JF - Annals of the American Thoracic Society

SN - 2325-6621

IS - 5

ER -