ATS 2021 will feature presentations of original research from accepted abstracts. Mini Symposia and Thematic Poster Sessions are abstract based sessions.
Please use the form below to browse scientific abstracts and case reports accepted for ATS 2021. Abstracts presented at the ATS 2021 will be published in the Online Abstract Issue of the American Journal of Respiratory and Critical Care Medicine, Volume 203, May 3, 2021.
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Risk of All-Cause Mortality During and After Severe Exacerbations in Patients with Chronic Obstructive Pulmonary Disease (COPD): Post Hoc Analysis of the IMPACT Trial
Session Title
TP40 - TP040 COPD CLINICAL TRIALS AND THERAPIES
Abstract
A2243 - Risk of All-Cause Mortality During and After Severe Exacerbations in Patients with Chronic Obstructive Pulmonary Disease (COPD): Post Hoc Analysis of the IMPACT Trial
Author Block: M. J. Mammen1, T. F. Carr2, G. J. Criner3, M. T. Dransfield4, D. M. G. Halpin5, M. K. Han6, B. Hartley7, R. Jain8, V. Kaul9, M. G. Kaye10, M. Kraft2, D. Mapel11, D. Midwinter12, P. D. Scanlon13, D. Singh14, J. M. Wells4, R. Wise15, D. A. Lipson16; 1Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, United States, 2Department of Medicine and Asthma and Airway Disease Research Center, University of Arizona College of Medicine, Tucson, AZ, United States, 3Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States, 4Division of Pulmonary, Allergy, and Critical Care Medicine, Lung Health Center, University of Alabama at Birmingham, Birmingham, AL, United States, 5University of Exeter Medical School, University of Exeter, Exeter, United Kingdom, 6University of Michigan, Pulmonary & Critical Care, Ann Arbor, MI, United States, 7Veramed Ltd, Twickenham, United Kingdom, 8GSK, Research Triangle Park, NC, United States, 9State University of New York Upstate Medical & Crouse Health, Syracuse, NY, United States, 10Minnesota Lung Center, Minneapolis, MN, United States, 11University of New Mexico College of Pharmacy, Albuquerque, NM, United States, 12GSK, Brentford, United Kingdom, 13Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, United States, 14University of Manchester, Manchester University NHS Foundation Trust, Manchester, United Kingdom, 15Johns Hopkins University School of Medicine, Baltimore, MD, United States, 16GSK & Perelman School of Medicine, University of Pennsylvania, Collegeville & Philadelphia, PA, United States.
Rationale: Severe exacerbations are associated with an increased risk of mortality in patients with chronic obstructive pulmonary disease (COPD). In the IMPACT trial, fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy was associated with a 34% reduction in the annual rate of severe exacerbations versus the long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) UMEC/VI in patients with symptomatic COPD and a history of exacerbations. Furthermore, FF/UMEC/VI also reduced on-treatment all-cause mortality (ACM) risk by 42% when compared with UMEC/VI. This analysis investigated the risk of ACM during and following a moderate or severe exacerbation in patients enrolled in the IMPACT trial.
Methods: IMPACT was a Phase III, randomized, double-blind, 52-week trial comparing once-daily FF/UMEC/VI 100/62.5/25 mcg with FF/VI 100/25 mcg and UMEC/VI 62.5/25 mcg. Eligible patients (≥40 years of age) had symptomatic COPD (COPD Assessment Test score ≥10), and a forced expiratory volume in 1 second (FEV1) <50% predicted and ≥1 moderate or severe exacerbation in the prior year, or a FEV1 50-<80% predicted and ≥2 moderate or ≥1 severe exacerbations in the prior year. This post hoc analysis analyzed the risk of on-treatment ACM during and 1-90 and 91-365 days post moderate or severe exacerbations, versus baseline using a time-dependent repeated measures Cox model. Moderate exacerbations were those requiring treatment with antibiotics or systemic/oral corticosteroids. Severe exacerbations were those resulting in hospitalization or death.
Results: 10,355 patients were included in the intent-to-treat population. 5034 (48.6%) patients experienced moderate/severe exacerbations. The risk of ACM was significantly increased during a severe exacerbation event compared with baseline (hazard ratio [HR] 41.22, 95% confidence interval [CI] 26.49, 64.15; P<0.001). This risk decreased post severe exacerbation, with neither time period demonstrating a significant difference in risk compared with the baseline period (1-90 days: HR 2.13, 95% CI 0.86, 5.29, P=0.102; 91-365 days: HR 1.15, 95% CI 0.27, 4.84, P=0.852; Figure 1). The risk of ACM during and 1-90 days following a moderate exacerbation was slightly elevated but did not reach statistical significance.
Conclusions: This time-dependent model analysis demonstrates that the risk of death was significantly increased during a severe exacerbation event in patients with symptomatic COPD and a history of exacerbations, with the risk of death decreasing following the severe exacerbation event. These results emphasize the importance of preventing severe exacerbations as a COPD treatment goal and the need to optimize treatment in patients at risk of exacerbations.
Funding: GSK (CTT116855/NCT02164513)
Author Block: M. J. Mammen1, T. F. Carr2, G. J. Criner3, M. T. Dransfield4, D. M. G. Halpin5, M. K. Han6, B. Hartley7, R. Jain8, V. Kaul9, M. G. Kaye10, M. Kraft2, D. Mapel11, D. Midwinter12, P. D. Scanlon13, D. Singh14, J. M. Wells4, R. Wise15, D. A. Lipson16; 1Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, United States, 2Department of Medicine and Asthma and Airway Disease Research Center, University of Arizona College of Medicine, Tucson, AZ, United States, 3Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States, 4Division of Pulmonary, Allergy, and Critical Care Medicine, Lung Health Center, University of Alabama at Birmingham, Birmingham, AL, United States, 5University of Exeter Medical School, University of Exeter, Exeter, United Kingdom, 6University of Michigan, Pulmonary & Critical Care, Ann Arbor, MI, United States, 7Veramed Ltd, Twickenham, United Kingdom, 8GSK, Research Triangle Park, NC, United States, 9State University of New York Upstate Medical & Crouse Health, Syracuse, NY, United States, 10Minnesota Lung Center, Minneapolis, MN, United States, 11University of New Mexico College of Pharmacy, Albuquerque, NM, United States, 12GSK, Brentford, United Kingdom, 13Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, United States, 14University of Manchester, Manchester University NHS Foundation Trust, Manchester, United Kingdom, 15Johns Hopkins University School of Medicine, Baltimore, MD, United States, 16GSK & Perelman School of Medicine, University of Pennsylvania, Collegeville & Philadelphia, PA, United States.
Rationale: Severe exacerbations are associated with an increased risk of mortality in patients with chronic obstructive pulmonary disease (COPD). In the IMPACT trial, fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy was associated with a 34% reduction in the annual rate of severe exacerbations versus the long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) UMEC/VI in patients with symptomatic COPD and a history of exacerbations. Furthermore, FF/UMEC/VI also reduced on-treatment all-cause mortality (ACM) risk by 42% when compared with UMEC/VI. This analysis investigated the risk of ACM during and following a moderate or severe exacerbation in patients enrolled in the IMPACT trial.
Methods: IMPACT was a Phase III, randomized, double-blind, 52-week trial comparing once-daily FF/UMEC/VI 100/62.5/25 mcg with FF/VI 100/25 mcg and UMEC/VI 62.5/25 mcg. Eligible patients (≥40 years of age) had symptomatic COPD (COPD Assessment Test score ≥10), and a forced expiratory volume in 1 second (FEV1) <50% predicted and ≥1 moderate or severe exacerbation in the prior year, or a FEV1 50-<80% predicted and ≥2 moderate or ≥1 severe exacerbations in the prior year. This post hoc analysis analyzed the risk of on-treatment ACM during and 1-90 and 91-365 days post moderate or severe exacerbations, versus baseline using a time-dependent repeated measures Cox model. Moderate exacerbations were those requiring treatment with antibiotics or systemic/oral corticosteroids. Severe exacerbations were those resulting in hospitalization or death.
Results: 10,355 patients were included in the intent-to-treat population. 5034 (48.6%) patients experienced moderate/severe exacerbations. The risk of ACM was significantly increased during a severe exacerbation event compared with baseline (hazard ratio [HR] 41.22, 95% confidence interval [CI] 26.49, 64.15; P<0.001). This risk decreased post severe exacerbation, with neither time period demonstrating a significant difference in risk compared with the baseline period (1-90 days: HR 2.13, 95% CI 0.86, 5.29, P=0.102; 91-365 days: HR 1.15, 95% CI 0.27, 4.84, P=0.852; Figure 1). The risk of ACM during and 1-90 days following a moderate exacerbation was slightly elevated but did not reach statistical significance.
Conclusions: This time-dependent model analysis demonstrates that the risk of death was significantly increased during a severe exacerbation event in patients with symptomatic COPD and a history of exacerbations, with the risk of death decreasing following the severe exacerbation event. These results emphasize the importance of preventing severe exacerbations as a COPD treatment goal and the need to optimize treatment in patients at risk of exacerbations.
Funding: GSK (CTT116855/NCT02164513)
