InforMing the PAthway of COPD Treatment (IMPACT Trial) Single-Inhaler Triple Therapy (Fluticasone Furoate/Umeclidinium/Vilanterol) Versus Fluticasone Furoate/Vilanterol and Umeclidinium/Vilanterol in Patients With COPD: Analysis of the Western Europe and North America Regions

Abstract

Background: The InforMing the Pathway of COPD Treatment (IMPACT) trial demonstrated lower moderate/severe exacerbation rates with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI or UMEC/VI in patients with chronic obstructive pulmonary disease (COPD) and a history of exacerbations. Since IMPACT was a global study, post-hoc analyses were conducted by geographic region to investigate potential differences in overall findings.

Methods: IMPACT was a 52-week, randomized, double-blind trial. Patients with symptomatic COPD and ≥1 moderate/severe exacerbation in the prior year were randomized 2:2:1 to once-daily FF/UMEC/VI 100/62.5/25µg, FF/VI 100/25µg, or UMEC/VI 62.5/25µg. Endpoints assessed in the overall, Western Europe and North America populations included on-treatment moderate/severe exacerbation (rates and time-to-first), trough forced expiratory volume in 1 second and St George's Respiratory Questionnaire (SGRQ) total score. Safety was assessed.

Results: Overall, 10,355 patients were enrolled, 3164 from Western Europe, 2639 from North America. FF/UMEC/VI significantly reduced on-treatment moderate/severe exacerbation rates versus FF/VI and UMEC/VI in Western Europe (rate ratios 0.82 [95%CI 0.74-0.91], P<.001 and 0.76 [0.67-0.87], P<.001) and in North America (0.87 [0.77-0.97], P=.014 and 0.69 [0.60-0.80], P<.001). FF/UMEC/VI reduced time-to-first moderate/severe exacerbation and improved lung function versus FF/VI and UMEC/VI in both regions, and improved SGRQ total score in Western Europe, but not North America. Safety profiles were generally similar between treatment groups/regions; the inhaled corticosteroid class effect of increased pneumonia incidence was seen in North America but not Western Europe.

Conclusion: Consistent with intent-to-treat results, FF/UMEC/VI reduced moderate/severe exacerbation rate and risk and improved lung function in Western Europe and North America; however, between-regions differences were seen for SGRQ total score and pneumonia incidence.

Clinical trial registration: NCT02164513.

Keywords: COPD; North America; Western Europe; exacerbations; single-inhaler triple therapy.

Conflict of interest statement

Editorial support (in the form of writing assistance, assembling figures, collating author comments, grammatical editing and referencing) was provided by Chrystelle Rasamison, Fishawack Indicia Ltd, United Kingdom, and was funded by GSK. A Bourdin was an investigator in the IMPACT trial and has received personal fees and a grant from Boehringer Ingelheim, personal fees from AstraZeneca, Chiesi, GSK, Novartis and Sanofi-Regeneron, and is an investigator in clinical trials from Nuvaira, Pulmonx, Actelion, MSD, United Therapeutic, Vertex, Acceleron, and Galapagos. G Criner has received personal fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, CSA Medical, Eolo, GSK, HGE Technologies, Novartis, Nuvaira, Olympus, Pulmonx, and Verona. G Devouassoux has received personal fees from AstraZeneca, Novartis Pharma, GSK, Chiesi, and Boehringer Ingelheim, and contracted clinical trial support from AstraZeneca, GSK, Novartis Pharma, ALK, Chiesi, and Boehringer Ingelheim. M Dransfield has received personal fees from Boehringer Ingelheim, PneumRx/BTG, Genentech, Quark Pharmaceuticals, Mereo, AstraZeneca and GSK, a grant from the Department of Defense, and contracted clinical trial support from PneumRx/BTG, Novartis, AstraZeneca, Yungjin, Pulmonx, Boston Scientific, Boehringer Ingelheim, and GSK. DMG Halpin reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, and Pfizer, and non-financial support Boehringer Ingelheim and Novartis. MK Han has received personal fees from AstraZeneca, Boehringer Ingelheim, Merck, Mylan and GSK and research support from Novartis and Sunovion. CE Jones, S Lettis, DA Lipson, N Martin, H Quasny, and L Sail are GSK employees and hold stock/shares in GSK. R Kalhan reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study, grants and personal fees from Boehringer Ingelheim, grants from PneumRx (BTG), grants from Spiration, grants and personal fees from AstraZeneca, personal fees from CVS Caremark, personal fees from Aptus Health, grants and personal fees from GSK, personal fees from Boston Scientific, and personal fees from Boston Consulting Group. P Lange reports personal fees from GSK, AstraZeneca, Chiesi and Boehringer Ingelheim, and grant support from Boehringer Ingelheim. DA Lomas reports personal fees from GSK and Grifols; he chaired the GSK Respiratory Therapy Area Board in 2012–2015. JM Echave-Sustaeta María-Tomé has received personal fees from GSK and was an investigator in the IMPACT trial. FJ Martinez has received personal fees and non-financial support from, AstraZeneca, Boehringer Ingelheim, Genentech, GSK, Inova Fairfax Health System, Miller Communications, National Society for Continuing Education, Novartis, Pearl Pharmaceuticals, PeerView Communications, Prime Communications, Puerto Rico Respiratory Society, Chiesi, Sunovion, Theravance, Potomac, University of Alabama-Birmingham, Physicians Education Resource, Canadian Respiratory Network, Teva and Dartmouth; and personal fees from Columbia University, MD Magazine, Methodist Hospital Brooklyn, New York University, UpToDate, WebMD/MedScape, Patara/Respivant, the American Thoracic Society, Rockpointe, Rare Disease Healthcare Communications and the France Foundation, and has taken part in advisory boards for AstraZeneca, Boehringer Ingelheim, ProterrixBio, Genentech, Novartis, Pearl Pharmaceuticals, Theravance, Zambon, Gala, Chiesi, GSK, Sunovion, and Teva, steering committees for AstraZeneca, Pearl Pharmaceuticals, Afferent/Merck, Gilead, Nitto, Patara/Respivant, Biogen, Veracyte, Prometic, Bayer, ProMedior and GSK, and been an advisor for Bridge Biotherapeutics. TM Siler has received research grants from AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, Compleware, Evidera (PPD), Forest Research Institute (now AstraZeneca), GSK, Novartis, Pearl Therapeutics, Proterix BioPharma, Oncocyte, Sanofi, Seer, Sunovion, Teva, Theravance BioPharma, Vapotherm, Restorbio and Westward, and personal fees from GSK, Sunovion, Theravance Biopharma and Vapotherm. D 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, Theravance and Verona. B Thomashow has taken part in advisory boards for AstraZeneca and GSK. H Watz reports personal fees from AstraZeneca, Boehringer Ingelheim, BerlinChemie, Chiesi, GSK, Novartis, Takeda, and Verona Pharma. R Wise reports personal fees from AstraZeneca/Medimmune/Pearl, Boehringer Ingelheim, Contrafect, Pulmonx, Roche, Spiration, Sunovion, Circassia, Pneuma, Verona, Mylan/Theravance, Propeller Health, AbbVie GSK, Merck, Kiniksa and Galderma, and has received research grants from AstraZeneca/MedImmune/Pearl, Boehringer Ingelheim, Pearl Therapeutics, Sanofi-Aventis and GSK. NA Hanania was an investigator on the IMPACT trial and reports receiving personal fees from GSK, AstraZeneca, Boehringer Ingelheim, Sanofi Genzyme, Novartis, Regeneron, Genentech, Sunovion, and Mylan. He also received research support from GSK, Boehringer Ingelheim, Sanofi Genzyme, Novartis and Astra Zeneca. ELLIPTA is owned by or licensed to the GSK Group of Companies.

JCOPDF © 2021.

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