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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An Analysis of the IMPACT Trial Assessing Single-Inhaler Therapy with Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) Versus FF/VI and UMEC/VI Using a Composite Adverse Event Outcome in Patients with COPD
Session Title
TP40 - TP040 COPD CLINICAL TRIALS AND THERAPIES
Abstract
A2240 - An Analysis of the IMPACT Trial Assessing Single-Inhaler Therapy with Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) Versus FF/VI and UMEC/VI Using a Composite Adverse Event Outcome in Patients with COPD
Author Block: J. M. Wells1, S. P. Bhatt1, T. F. Carr2, G. J. Criner3, D. M. G. Halpin4, M. K. Han5, R. Jain6, M. G. Kaye7, M. Kraft2, D. A. Lipson8, D. Mapel9, M. J. Mammen10, C. McEvoy11, D. Midwinter12, D. Singh13, R. Wise14, M. T. Dransfield1; 1Division of Pulmonary, Allergy, and Critical Care Medicine, Lung Health Center, University of Alabama at Birmingham, Birmingham, AL, 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, 4University of Exeter Medical School, University of Exeter, Exeter, United Kingdom, 5University of Michigan, Pulmonary & Critical Care, Ann Arbor, MI, United States, 6GSK, Research Triangle Park, NC, United States, 7Minnesota Lung Center, Minneapolis, MN, United States, 8GSK & Perelman School of Medicine, University of Pennsylvania, Collegeville & Philadelphia, PA, United States, 9University of New Mexico College of Pharmacy, Albuquerque, NM, United States, 10Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, United States, 11HealthPartners Institute for Education and Research, Bloomington, MN, United States, 12GSK, Brentford, United Kingdom, 13University of Manchester, Manchester University NHS Foundation Trust, Manchester, United Kingdom, 14Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Rationale
The IMPACT trial demonstrated that fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) single-inhaler triple therapy significantly reduced severe exacerbations rates and all-cause mortality risk versus UMEC/VI in patients with chronic obstructive pulmonary disease (COPD). However, concerns have been raised about an increased risk of pneumonia with inhaled corticosteroid-containing regimens as well as cardiovascular effects with dual bronchodilation. To better determine the benefit-risk profile of FF/UMEC/VI versus FF/VI and UMEC/VI in the IMPACT population, a composite adverse event outcome was examined.
Methods
The IMPACT trial (NCT02164513, CTT116855) was a 52-week, randomized, double-blind, multicenter study comparing FF/UMEC/VI 100/62.5/25µg with FF/VI 100/25µg and UMEC/VI 62.5/25µg in patients aged ≥40 years with symptomatic COPD (COPD Assessment Test score ≥10) and forced expiratory volume in 1 second (FEV1) <50% predicted and ≥1 moderate or severe exacerbation in the prior year, or FEV1 50-<80% predicted and ≥2 moderate or ≥1 severe exacerbations in the prior year. This post hoc analysis evaluated time-to-first composite event, comprising on-treatment severe exacerbation, on-treatment cardiovascular adverse event of special interest (AESI) resulting in hospitalization or death, on-treatment pneumonia AESI resulting in hospitalization or death, or on-treatment death from any cause. For patients with multiple events, only the first event contributed to this analysis. Severe exacerbations were defined as worsening of symptoms resulting in hospitalization or death. The analysis was conducted using a Cox proportional hazards model with covariates of treatment group, sex, exacerbation history (≤1, ≥2 moderate/severe), geographical region, smoking status (screening) and post bronchodilator percent predicted FEV1 (screening).
Results
The overall intent-to-treat population comprised 10,355 patients (FF/UMEC/VI, n=4151; FF/VI, n=4134; UMEC/VI, n=2070). Composite events occurred in 647 (16%), 636 (15%), and 356 (17%) patients receiving FF/UMEC/VI, FF/VI, and UMEC/VI, respectively. The probability of experiencing an event before Day 365 with FF/UMEC/VI, FF/VI, and UMEC/VI was 16.7%, 17.5%, and 19.1%, respectively (Figure). FF/UMEC/VI significantly reduced composite event risk versus UMEC/VI by 16.5% (95% confidence interval [CI]: 5.0, 26.7; p=0.006). The point estimates for the reduction in the risk of a composite event favored FF/UMEC/VI over FF/VI (6.2% reduction [-4.7, 15.9]; p=0.255), and FF/VI over UMEC/VI (11.1% reduction [-1.3, 21.9]; p=0.077), but differences were not statistically significant.
Conclusions
FF/UMEC/VI significantly reduced the risk of a composite adverse event versus UMEC/VI and numerically reduced the risk versus FF/VI, demonstrating a favorable benefit-risk profile of once-daily FF/UMEC/VI triple therapy compared with dual therapy in patients with symptomatic COPD and a history of exacerbations.
Funding
GSK (NCT02164513/CTT116855).
Author Block: J. M. Wells1, S. P. Bhatt1, T. F. Carr2, G. J. Criner3, D. M. G. Halpin4, M. K. Han5, R. Jain6, M. G. Kaye7, M. Kraft2, D. A. Lipson8, D. Mapel9, M. J. Mammen10, C. McEvoy11, D. Midwinter12, D. Singh13, R. Wise14, M. T. Dransfield1; 1Division of Pulmonary, Allergy, and Critical Care Medicine, Lung Health Center, University of Alabama at Birmingham, Birmingham, AL, 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, 4University of Exeter Medical School, University of Exeter, Exeter, United Kingdom, 5University of Michigan, Pulmonary & Critical Care, Ann Arbor, MI, United States, 6GSK, Research Triangle Park, NC, United States, 7Minnesota Lung Center, Minneapolis, MN, United States, 8GSK & Perelman School of Medicine, University of Pennsylvania, Collegeville & Philadelphia, PA, United States, 9University of New Mexico College of Pharmacy, Albuquerque, NM, United States, 10Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, United States, 11HealthPartners Institute for Education and Research, Bloomington, MN, United States, 12GSK, Brentford, United Kingdom, 13University of Manchester, Manchester University NHS Foundation Trust, Manchester, United Kingdom, 14Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Rationale
The IMPACT trial demonstrated that fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) single-inhaler triple therapy significantly reduced severe exacerbations rates and all-cause mortality risk versus UMEC/VI in patients with chronic obstructive pulmonary disease (COPD). However, concerns have been raised about an increased risk of pneumonia with inhaled corticosteroid-containing regimens as well as cardiovascular effects with dual bronchodilation. To better determine the benefit-risk profile of FF/UMEC/VI versus FF/VI and UMEC/VI in the IMPACT population, a composite adverse event outcome was examined.
Methods
The IMPACT trial (NCT02164513, CTT116855) was a 52-week, randomized, double-blind, multicenter study comparing FF/UMEC/VI 100/62.5/25µg with FF/VI 100/25µg and UMEC/VI 62.5/25µg in patients aged ≥40 years with symptomatic COPD (COPD Assessment Test score ≥10) and forced expiratory volume in 1 second (FEV1) <50% predicted and ≥1 moderate or severe exacerbation in the prior year, or FEV1 50-<80% predicted and ≥2 moderate or ≥1 severe exacerbations in the prior year. This post hoc analysis evaluated time-to-first composite event, comprising on-treatment severe exacerbation, on-treatment cardiovascular adverse event of special interest (AESI) resulting in hospitalization or death, on-treatment pneumonia AESI resulting in hospitalization or death, or on-treatment death from any cause. For patients with multiple events, only the first event contributed to this analysis. Severe exacerbations were defined as worsening of symptoms resulting in hospitalization or death. The analysis was conducted using a Cox proportional hazards model with covariates of treatment group, sex, exacerbation history (≤1, ≥2 moderate/severe), geographical region, smoking status (screening) and post bronchodilator percent predicted FEV1 (screening).
Results
The overall intent-to-treat population comprised 10,355 patients (FF/UMEC/VI, n=4151; FF/VI, n=4134; UMEC/VI, n=2070). Composite events occurred in 647 (16%), 636 (15%), and 356 (17%) patients receiving FF/UMEC/VI, FF/VI, and UMEC/VI, respectively. The probability of experiencing an event before Day 365 with FF/UMEC/VI, FF/VI, and UMEC/VI was 16.7%, 17.5%, and 19.1%, respectively (Figure). FF/UMEC/VI significantly reduced composite event risk versus UMEC/VI by 16.5% (95% confidence interval [CI]: 5.0, 26.7; p=0.006). The point estimates for the reduction in the risk of a composite event favored FF/UMEC/VI over FF/VI (6.2% reduction [-4.7, 15.9]; p=0.255), and FF/VI over UMEC/VI (11.1% reduction [-1.3, 21.9]; p=0.077), but differences were not statistically significant.
Conclusions
FF/UMEC/VI significantly reduced the risk of a composite adverse event versus UMEC/VI and numerically reduced the risk versus FF/VI, demonstrating a favorable benefit-risk profile of once-daily FF/UMEC/VI triple therapy compared with dual therapy in patients with symptomatic COPD and a history of exacerbations.
Funding
GSK (NCT02164513/CTT116855).
