Risk of Exacerbation and Pneumonia with Single-Inhaler Triple versus Dual Therapy in IMPACT
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
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 › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
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 -
ID: 269793864