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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All-Cause Mortality by Subgroup in Patients with Chronic Obstructive Pulmonary Disease: Post Hoc Analysis of the IMPACT Trial
Session Title
TP40 - TP040 COPD CLINICAL TRIALS AND THERAPIES
Abstract
A2241 - All-Cause Mortality by Subgroup in Patients with Chronic Obstructive Pulmonary Disease: 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, R. G. Jain7, V. Kaul8, M. G. Kaye9, M. Kraft2, D. Mapel10, D. Midwinter11, P. D. Scanlon12, D. Singh13, J. M. Wells4, R. Wise14, D. A. Lipson15; 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, 7GSK, Research Triangle Park, NC, United States, 8State University of New York Upstate Medical & Crouse Health, Syracuse, NY, United States, 9Minnesota Lung Center, Minneapolis, MN, United States, 10University of New Mexico College of Pharmacy, Albuquerque, NM, United States, 11GSK, Brentford, United Kingdom, 12Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, United States, 13University of Manchester, Manchester University NHS Foundation Trust, Manchester, United Kingdom, 14Johns Hopkins University School of Medicine, Baltimore, MD, United States, 15GSK & Perelman School of Medicine, University of Pennsylvania, Collegeville & Philadelphia, PA, United States.
Rationale: The IMPACT trial demonstrated a significant reduction in on-/off-treatment all-cause mortality (ACM) risk with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease (COPD) and a history of exacerbations. To identify whether this mortality benefit finding was associated with specific patient characteristics, the time to on-/off-treatment ACM by patient subgroups was investigated.
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 (aged ≥40 years) 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 time to on-/off-treatment ACM, including additional vital status data, for FF/UMEC/VI versus UMEC/VI using a Cox proportional hazards model with covariates of treatment group, age (at screening), and sex. On-/off-treatment deaths were defined as those occurring between study treatment start date and the latest of study treatment stop date or projected Week 52 date (based on treatment start date) +7 days, inclusive. Subgroups included pneumonia history, cardiovascular risk, smoking status, age, sex, body mass index, race, geographical region, and exacerbation history in the prior year.
Results: The intent-to-treat (ITT) population comprised 10,355 patients (FF/UMEC/VI, n=4151; FF/VI n=4134; UMEC/VI, n=2070); vital status at Week 52 was obtained for 99.6% of the ITT population. There were 98 (2.36%) and 66 (3.19%) on-/off-treatment deaths reported in the FF/UMEC/VI and UMEC/VI arms, respectively. FF/UMEC/VI demonstrated a significant reduced risk of on-/off-treatment ACM compared with UMEC/VI in some subgroups, including patients with ≥2 cardiovascular risk factors (39.4% reduction; 95% confidence interval [CI]: 7.1, 60.5; P=0.022), a past history of pneumonia (49.1% reduction; 95% CI: 10.4, 71.1; P=0.019), or with <2 moderate/severe exacerbations (42.1% reduction; 95% CI: 7.3, 63.8; P=0.023) (Figure 1).
Conclusions: This post hoc analysis examined multiple patient subgroups representing predefined demographics and baseline disease characteristics. The mortality reduction was generally consistent across subgroups with none disproportionately contributing to the overall on-/off-treatment ACM benefits for FF/UMEC/VI versus UMEC/VI seen in the IMPACT trial. However, the small number of events in some patient subgroups limits the interpretation of these findings.
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, R. G. Jain7, V. Kaul8, M. G. Kaye9, M. Kraft2, D. Mapel10, D. Midwinter11, P. D. Scanlon12, D. Singh13, J. M. Wells4, R. Wise14, D. A. Lipson15; 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, 7GSK, Research Triangle Park, NC, United States, 8State University of New York Upstate Medical & Crouse Health, Syracuse, NY, United States, 9Minnesota Lung Center, Minneapolis, MN, United States, 10University of New Mexico College of Pharmacy, Albuquerque, NM, United States, 11GSK, Brentford, United Kingdom, 12Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, United States, 13University of Manchester, Manchester University NHS Foundation Trust, Manchester, United Kingdom, 14Johns Hopkins University School of Medicine, Baltimore, MD, United States, 15GSK & Perelman School of Medicine, University of Pennsylvania, Collegeville & Philadelphia, PA, United States.
Rationale: The IMPACT trial demonstrated a significant reduction in on-/off-treatment all-cause mortality (ACM) risk with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease (COPD) and a history of exacerbations. To identify whether this mortality benefit finding was associated with specific patient characteristics, the time to on-/off-treatment ACM by patient subgroups was investigated.
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 (aged ≥40 years) 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 time to on-/off-treatment ACM, including additional vital status data, for FF/UMEC/VI versus UMEC/VI using a Cox proportional hazards model with covariates of treatment group, age (at screening), and sex. On-/off-treatment deaths were defined as those occurring between study treatment start date and the latest of study treatment stop date or projected Week 52 date (based on treatment start date) +7 days, inclusive. Subgroups included pneumonia history, cardiovascular risk, smoking status, age, sex, body mass index, race, geographical region, and exacerbation history in the prior year.
Results: The intent-to-treat (ITT) population comprised 10,355 patients (FF/UMEC/VI, n=4151; FF/VI n=4134; UMEC/VI, n=2070); vital status at Week 52 was obtained for 99.6% of the ITT population. There were 98 (2.36%) and 66 (3.19%) on-/off-treatment deaths reported in the FF/UMEC/VI and UMEC/VI arms, respectively. FF/UMEC/VI demonstrated a significant reduced risk of on-/off-treatment ACM compared with UMEC/VI in some subgroups, including patients with ≥2 cardiovascular risk factors (39.4% reduction; 95% confidence interval [CI]: 7.1, 60.5; P=0.022), a past history of pneumonia (49.1% reduction; 95% CI: 10.4, 71.1; P=0.019), or with <2 moderate/severe exacerbations (42.1% reduction; 95% CI: 7.3, 63.8; P=0.023) (Figure 1).
Conclusions: This post hoc analysis examined multiple patient subgroups representing predefined demographics and baseline disease characteristics. The mortality reduction was generally consistent across subgroups with none disproportionately contributing to the overall on-/off-treatment ACM benefits for FF/UMEC/VI versus UMEC/VI seen in the IMPACT trial. However, the small number of events in some patient subgroups limits the interpretation of these findings.
Funding: GSK (CTT116855/NCT02164513)
