Abstract
Introduction Clinically important deterioration (CID) is a multicomponent measure for assessing disease worsening in chronic obstructive pulmonary disease (COPD). This analysis investigated the prognostic value of a CID event on future clinical outcomes, and effect of single-inhaler triple versus dual therapy on reducing CID risk in patients in the IMPACT trial.
Methods IMPACT was a Phase III, double-blind, 52-week multicenter trial. Patients with symptomatic COPD and ≥1 moderate/severe exacerbation in the prior year were randomised 2:2:1 to fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 µg, FF/VI 100/25 µg, or UMEC/VI 62.5/25 µg. CID at the timepoint of interest was defined as: a moderate/severe exacerbation, or ≥100 mL decrease in trough forced expiratory volume in 1 s or deterioration in health status (≥4.0 unit increase in St George's Respiratory Questionnaire total score or ≥2.0 unit increase in COPD Assessment Test score) from baseline. A treatment-independent post hoc prognostic analysis compared clinical outcomes up to Week 52 in patients with/without a CID by Week 28. A prospective analysis evaluated time-to-first CID with each treatment.
Results Patients with a CID by Week 28 had significantly increased exacerbation rates after Week 28, smaller improvements in lung function and health status at Week 52 (all p<0.001), and increased risk of all-cause mortality after Week 28 versus patients who were CID-free. FF/UMEC/VI significantly reduced CID risk versus dual therapies (all p<0.001).
Conclusions Prevention of short-term disease worsening was associated with better long-term clinical outcomes. FF/UMEC/VI reduced CID risk versus dual therapies; this effect may improve long-term prognosis in this population.
Funding GSK (CTT116855/NCT02164513).
Footnotes
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Conflict of interest: Dr. Han reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from GlaxoSmithKline, other from Novartis, other from Sunovion, personal fees from Mylan, personal fees from Merck, personal fees from Verona, outside the submitted work;.
Conflict of interest: Dr. Criner reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; personal fees from Almirall, personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Chiesi, personal fees from CSA Medical, personal fees from Eolo Medical, personal fees from GlaxoSmithKline, other from HGE Health Care Solutions, personal fees from Novartis, personal fees from Nuvaira, personal fees from Olympus, personal fees from Pulmonx, personal fees from Verona, personal fees from Amgen, personal fees from Broncus Medical, personal fees from Gala Therapeutics, personal fees from Helios Medical, personal fees from Merck, personal fees from Medtronic, personal fees from Mereo BioPharma, personal fees from NGM Biopharmaceuticals, personal fees from Philips Respironics, personal fees from Respivant Sciences, personal fees from The Implementation Group, outside the submitted work;.
Conflict of interest: Dr. Dransfield reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; grants from Department of Defense, personal fees and other from Boehringer Ingelheim, personal fees and other from GlaxoSmithKline, other from Novartis, personal fees and other from AstraZeneca, other from Yungjin, personal fees and other from PneumRx/BTG, other from Pulmonx, personal fees from Genentech, other from Boston Scientific, personal fees from Quark Pharmaceuticals, grants from NIH, personal fees from Mereo, grants from American Lung Association, grants from NIH, outside the submitted work;.
Conflict of interest: Dr. Halpin reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; personal fees from AstraZeneca, personal fees and non-financial support from Boehringer Ingelheim, personal fees from Chiesi, personal fees and non-financial support from GlaxoSmithKline, personal fees from Novartis, personal fees from Pfizer, personal fees from Sanofi, outside the submitted work;.
Conflict of interest: Dr. Jones reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; other from GlaxoSmithKline, other from GlaxoSmithKline, outside the submitted work;.
Conflict of interest: Dr. Kilbride reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; other from GlaxoSmithKline, other from GlaxoSmithKline, outside the submitted work;.
Conflict of interest: Dr. Lange reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Chiesi, grants and personal fees from GlaxoSmithKline, outside the submitted work;.
Conflict of interest: Dr. Lettis reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; other from GlaxoSmithKline, other from GlaxoSmithKline, outside the submitted work;.
Conflict of interest: Dr. Lipson reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; other from GlaxoSmithKline, other from GlaxoSmithKline, outside the submitted work;.
Conflict of interest: Dr. Lomas reports personal fees and other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; grants from GlaxoSmithKline, personal fees from Griffols, outside the submitted work;.
Conflict of interest: Dr. Martin reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; other from GlaxoSmithKline, other from GlaxoSmithKline, outside the submitted work;.
Conflict of interest: Dr. Martinez reports grants and other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; personal fees, non-financial support and other from AstraZeneca, personal fees, non-financial support and other from Boehringer Ingelheim, non-financial support and other from ProterrixBio, personal fees from Columbia University, personal fees and non-financial support from Genentech, personal fees and non-financial support from GlaxoSmithKline, personal fees and non-financial support from Inova Fairfax Health System, personal fees from MD Magazine, personal fees from Methodist Hospital Brooklyn, personal fees and non-financial support from Miller Communications, personal fees and non-financial support from National Association for Continuing Education, personal fees and non-financial support from Novartis, personal fees from New York University, personal fees and non-financial support from Pearl Pharmaceuticals, personal fees and non-financial support from PeerView Communications, personal fees and non-financial support from Prime Communications, personal fees and non-financial support from Puerto Rican Respiratory Society, personal fees and non-financial support from Chiesi, personal fees and non-financial support from Sunovion, personal fees and non-financial support from Theravance, personal fees from UpToDate, personal fees from WebMD/MedScape, other from Afferent/Merck, non-financial support from Gilead, non-financial support from Nitto, personal fees and other from Patara/Respivant, personal fees and non-financial support from Potomac, other from Biogen, personal fees and non-financial support from University of Alabama Birmingham, other from Veracyte, non-financial support from Zambon, personal fees from American Thoracic Society, grants from NIH, personal fees and non-financial support from Physicians Education Resource, personal fees from Rockpointe, other from Prometic, personal fees from Rare Disease Healthcare Communications, other from Bayer, other from Bridge Biotherapeutics, personal fees and non-financial support from Canadian Respiratory Network, other from ProMedior, personal fees and non-financial support from Teva, personal fees from France Foundation, personal fees and non-financial support from Dartmouth, other from Gala, personal fees from Physicians Education Resource, outside the submitted work;.
Conflict of interest: Dr. Wise reports personal fees, non-financial support and other from GlaxoSmithKline, during the conduct of the study; grants and personal fees from AstraZeneca / Medimmune / Pearl, grants and personal fees from Boehringer Ingelheim, personal fees from Contrafect, personal fees from Pulmonx, personal fees from Roche, personal fees from Spiration, personal fees from Sunovion, grants from Pearl Therapeutics, personal fees from Merck, personal fees from Circassia, personal fees from Pneuma, personal fees from Verona, personal fees from Mylan/Theravance, personal fees from Propeller Health, grants from Sanofi-Aventis, personal fees from AbbVie, grants and personal fees from GSK, outside the submitted work;.
Conflict of interest: Dr. Naya reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; other from GlaxoSmithKline, outside the submitted work;.
Conflict of interest: Dr. Singh reports other from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; grants and personal fees from AstraZeneca, grants and personal fees from Boehringer Ingelheim, grants and personal fees from Chiesi, personal fees from Cipla, personal fees from Genentech, grants and personal fees from Glenmark, personal fees from GlaxoSmithKline, grants and personal fees from Menarini, grants and personal fees from Mundipharma, grants and personal fees from Novartis, personal fees from Peptinnovate, grants and personal fees from Pfizer, grants and personal fees from Pulmatrix, grants and personal fees from Theravance, grants and personal fees from Verona, outside the submitted work;.
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- Received November 26, 2020.
- Accepted December 8, 2020.
- Copyright ©ERS 2021
This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.
