Higher COPD Assessment Test Score Associated With Greater Exacerbations Risk: A Post Hoc Analysis of the IMPACT Trial

Abstract

Background: In the InforMing the PAthway of COPD Treatment (IMPACT) trial, single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) reduced moderate/severe exacerbation rates versus FF/VI and UMEC/VI in patients with chronic obstructive pulmonary disease (COPD). This post hoc analysis tested the relationship between baseline health status, risk of future exacerbations, and efficacy outcomes.

Methods: IMPACT was a Phase 3, double-blind, 52-week trial in patients with symptomatic COPD (COPD Assessment Test [CAT] score ≥10) and ≥1 moderate/severe exacerbation in the prior year randomized 2:2:1 to FF/UMEC/VI 100/62.5/25mcg, FF/VI 100/25mcg, or UMEC/VI 62.5/25mcg. Annual rate of on-treatment moderate/severe exacerbations, lung function, and safety were analyzed by continuous baseline CAT score.

Results: Moderate/severe exacerbation rates increased with increasing baseline CAT scores in FF/UMEC/VI and UMEC/VI arms. There was a very small increase in on-treatment pneumonia rates at higher baseline CAT scores across all treatment arms. FF/UMEC/VI reduced moderate/severe exacerbation rates versus UMEC/VI (i.e., the inhaled corticosteroid effect) consistently across the range of CAT scores. The reduction with FF/UMEC/VI versus FF/VI (i.e., the long-acting muscarinic antagonist effect) was greatest at lower CAT scores and appeared lesser at higher CAT scores. Improvements in lung function were observed with FF/UMEC/VI versus FF/VI and UMEC/VI, regardless of baseline CAT score.

Conclusions: The CAT score was predictive of exacerbation risk. Worse baseline health status was associated with higher moderate/severe exacerbation and pneumonia rates. Irrespective of baseline CAT score, FF/UMEC/VI improved lung function, and reduced the annual moderate/severe exacerbation rates versus dual therapy. Results indicate an overall favorable benefit-risk profile of triple versus dual therapy, irrespective of CAT score. Clinical Trial Registration:GSK (CTT116855/NCT02164513).

Keywords: COPD Assessment Test; IMPACT trial; exacerbations; patient-reported outcomes; single-inhaler triple therapy.

Conflict of interest statement

All authors report other and non-financial support from GlaxoSmithKline (GSK) (funding the study and funding medical writing support by Katie Baker and Eloise Morecroft at Fishawack Indicia Ltd, United Kingdom). Marjorie Stiegler, Dawn Midwinter, and David A. Lipson are GSK employees and hold stock/shares in GSK. Paul Jones and Maggie Tabberer were employed by GSK at the time of the study and hold stocks/shares in GSK. Gerard J. Criner has received personal fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, CSA Medical, Eolo, GSK, HGE Technologies, Novartis, Nuvaira, Olympus, Pulmonx, and Verona. Mark T. Dransfield is the editor-in-chief for Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation and has received personal fees and contracted clinical trial support from AstraZeneca and GSK, and personal fees from Teva and Pulmonx. MeiLan K. Han reports personal fees from GSK, AstraZeneca, Boehringer Ingelheim, Cipla, Chiesi, Novartis, Pulmonx, Teva, Verona, Merck, Mylan, Sanofi, DevPro, Aerogen, Polarian, Regeneron, United Therapeutics, Medscape, and Integrity. She has received either in-kind research support or funds paid to the institution from the National Institutes of Health, Novartis, Sunovion, Nuvaira, Sanofi, Astrazeneca, Boehringer Ingelheim, Gala Therapeutics, Biodesix, the COPD Foundation, and the American Lung Association. She has participated in data safety monitoring boards for Novartis and Medtronic with funds paid to the institution. She has received stock options from Meissa Vaccines. David M.G Halpin reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, and Pfizer, and non-financial support from Boehringer Ingelheim and Novartis. Peter Lange has received personal fees from GSK, AstraZeneca, and Boehringer Ingelheim, and grant support from Boehringer Ingelheim and GSK. Fernando J. Martinez reports personal fees and non-financial support from AstraZeneca, Boehringer Ingelheim, Chiesi, Genentech/Roche, GSK, Sunovion, and Teva, non-financial support from ProterrixBio, and other support from AstraZeneca, Boehringer Ingelheim, ProterrixBio. Dave Singh reports personal fees from GSK, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Genentech, Glenmark, Menarini, Mundipharma, Novartis, Peptinnovate, Pfizer, Pulmatrix, Theravance, and Verona, and grant support from AstraZeneca, Boehringer Ingelheim, Chiesi, Glenmark, Menarini, Mundipharma, Novartis, Pfizer, Pulmatrix, Therevance, and Verona. Dave Singh is supported by the National Institute for Health Research Manchester Biomedical Research Centre. Robert A. Wise has received personal fees from Boehringer Ingelheim, Contrafect, AstraZeneca, GSK, Merck, Verona, Mylan/Theravance, Propeller Health, Novartis, Bristol Myers Squibb, Galderma, Kiniksa, ChimiRx, and PureTech and grant support from Boehringer Ingelheim, AstraZeneca, Sanofi, Verona, and GSK. Byron Thomashow has taken part in advisory boards for AstraZeneca, Boehringer Ingelheim, and GSK, and has received personal fees for consultancy from GSK. ELLIPTA is owned by or licensed to the GSK Group of Companies.

Editorial support (in the form of writing assistance, including preparation of the draft manuscript under the direction and guidance of the authors, collating and incorporating authors’ comments for each draft, assembling tables and figures, grammatical editing, and referencing) was provided by Katie Baker, at Fishawack Indicia Ltd., United Kingdom, part of Fishawack Health, and was funded by GSK.

JCOPDF © 2021.

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