TY - JOUR
T1 - Effect of Age on the Efficacy and Safety of Once-Daily Single-Inhaler Triple-Therapy Fluticasone Furoate/Umeclidinium/Vilanterol in Patients With COPD
T2 - A Post Hoc Analysis of the Informing the Pathway of COPD Treatment Trial
AU - Hanania, Nicola A.
AU - Mannino, David M.
AU - Criner, Gerard J.
AU - Dransfield, Mark T.
AU - Han, Mei Lan K.
AU - Jones, C. Elaine
AU - Kilbride, Sally
AU - Lomas, David A.
AU - Martin, Neil
AU - Martinez, Fernando J.
AU - Singh, Dave
AU - Wise, Robert A.
AU - Halpin, David M.G.
AU - Lima, Robson
AU - Lipson, David A.
N1 - Funding Information:
FUNDING/SUPPORT: This study was funded by GlaxoSmithKline [GSK study number CTT116855; NCT02164513].Author contributions: The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. D. A. L. takes responsibility for the integrity of the work as a whole. All authors had full access to the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis. All authors contributed to data analysis and interpretation. N. A. H. G. J. C. M. T. D. and D. M. G. H. contributed to the acquisition of data and data analysis and interpretation. D. A. L. contributed to study conception and design and data analysis and interpretation. All authors contributed to the writing and reviewing of the manuscript and have given final approval for the version to be published. Financial/nonfinancial disclosures: The authors have reported to CHEST the following: N. A. H. was an investigator on the Informing the Pathway of COPD Treatment study and reports receiving personal fees from AstraZeneca plc; Boehringer Ingelheim; Genentech, Inc; GlaxoSmithKline (GSK); Mylan NV; Novartis; Regeneron Pharmaceuticals, Inc; Sanofi Genzyme; and Sunovion Pharmaceuticals, Inc for serving as an advisor or consultant. He also received research support from AstraZeneca plc, Boehringer Ingelheim, and GSK. D. M. M. C. E. J. S. K. N. M. R. L. and D. A. L. are GSK employees and hold stock and/or shares in GSK. G. C. has received personal fees from Almirall, SA; AstraZeneca plc; Boehringer Ingelheim; Chiesi USA, Inc; CSA Medical, Inc; Eolo Pharma; GSK; HGE Technologies; Novartis; Nuvaira, Inc; Olympus; Pulmonx Corporation; and Verona Pharma plc. M. T. D. has received personal fees from AstraZeneca plc and GSK and contracted clinical trial support from AstraZeneca plc, Boehringer Ingelheim, and GSK. M. K. H. has received personal fees from AstraZeneca plc, Boehringer Ingelheim, GSK, Merck & Co, and Mylan NV and research support from Novartis and Sunovion Pharmaceuticals, Inc. D. A. L. has received personal fees from Grifols and GSK and has received grant support from GSK. F. J. M. has taken part in advisory boards for AstraZeneca plc; Boehringer Ingelheim; Chiesi USA, Inc; GSK; Sunovion Pharmaceuticals, Inc; and Teva Pharmaceutical Industries Ltd; steering committees for AstraZeneca plc and GSK; and data and safety monitoring boards for Genentech, Inc/Roche and GSK and has been an advisor for ProTerrix Bio. D. S. reports personal fees from AstraZeneca plc; Boehringer Ingelheim; Chiesi USA, Inc; Cipla Limited; Genentech, Inc; Glenmark Pharmaceuticals Limited; GSK; Menarini Group; Mundipharma International Limited; Novartis; Peptinnovate Ltd; Pfizer, Inc; Pulmatrix, Inc; Theravance Biopharma, Inc; and Verona Pharma plc and grant support from AstraZeneca plc; Boehringer Ingelheim; Chiesi USA, Inc; Glenmark Pharmaceuticals Limited; Menarini Group; Mundipharma International Limited; Novartis; Pfizer, Inc; Pulmatrix, Inc; Theravance Biopharma, Inc; and Verona Pharma plc. R. A. W. has received personal fees from AbbVie, Inc; AstraZeneca plc/MedImmune/Pearl Therapeutics; Boehringer Ingelheim; Circassia Pharmaceuticals plc; ContraFect Corporation; Galderma SA; GSK; Kiniksa Pharmaceuticals, Ltd; Merck & Co; Mylan NV/Theravance Biopharma, Inc; Pneuma Respiratory, Inc; Propeller Health; Pulmonx Corporation; Roche; Spiration, Inc; Sunovion Pharmaceuticals, Inc; and Verona Pharma plc and has received research grants from AstraZeneca plc/MedImmune/Pearl Therapeutics, Boehringer Ingelheim, GSK, Pearl Therapeutics, and Sanofi-Aventis. D. M. G. H. reports personal fees from AstraZeneca plc; Boehringer Ingelheim; Chiesi USA, Inc; GSK; Novartis; Pfizer, Inc; and Sanofi and nonfinancial support from Boehringer Ingelheim and Novartis. Ellipta is owned by or licensed to the GSK Group of Companies. Role of sponsors: The funders of the study had a role in the study design, data analysis, data interpretation, and writing of the report. Other contributions: The authors thank Tedi Soule, PharmD, for her assistance with the interpretation of key data and for her contributions to the writing and reviewing of the manuscript. Editorial support (in the form of writing assistance, assembling figures, collating author comments, grammatical editing, and referencing) was provided by Katie Baker, PhD, and Hayley Mukherjee, PhD, at Fishawack Indicia Ltd, UK, part of Fishawack Health and was funded by GSK. Data availability: Anonymized individual participant data and study documents can be requested for further research from www.clinicalstudydatarequest.com. Additional information: The e-Appendix and e-Tables can be found in the Supplemental Materials section of the online article.
Funding Information:
FUNDING/SUPPORT: This study was funded by GlaxoSmithKline [GSK study number CTT116855; NCT02164513].
Publisher Copyright:
© 2020
PY - 2021/3
Y1 - 2021/3
N2 - Background: In the Informing the Pathway of COPD Treatment (IMPACT) trial, single-inhaler triple-therapy fluticasone furoate (FF), umeclidinium (UMEC), and vilanterol (VI) reduced moderate/severe exacerbation rates vs FF/VI and UMEC/VI in patients with symptomatic COPD and a history of exacerbations, with a similar safety profile. Research Question: Are trial outcomes with single-inhaler triple-therapy FF/UMEC/VI vs FF/VI and UMEC/VI affected by age in patients with symptomatic COPD and a history of exacerbations? Study Design and Methods: IMPACT was a phase III, double-blind, 52-week trial. Patients ≥ 40 years of age with symptomatic COPD and ≥ 1 moderate/severe exacerbation in the previous year were randomly assigned 2:2:1 to FF/UMEC/VI 100/62.5/25 μg, FF/VI 100/25 μg, or UMEC/VI 62.5/25 μg. End points assessed by age included annual rate of moderate/severe exacerbations, change from baseline (CFB) in trough FEV1, proportion of St. George's Respiratory Questionnaire (SGRQ) responders (≥ 4 units decrease from baseline in SGRQ total score), and safety. Results: The intention-to-treat population comprised 10,355 patients; 4,724 (46%), 4,225 (41%), and 1,406 (14%) were ≤ 64, 65 to 74, and ≥ 75 years of age, respectively. FF/UMEC/VI reduced on-treatment moderate/severe exacerbation rates vs FF/VI (% reduction [95% CI]: ≤ 64 years, 8% [−1 to 16]; P = .070; 65-74 years, 22% [14-29]; P < .001; ≥ 75 years, 18% [3-31]; P = .021) and vs UMEC/VI (≤ 64 years, 16% [7-25]; P = .002; 65-74 years, 33% [25-41]; P < .001; ≥ 75 years, 24% [6-38]; P = .012), with greatest rate reduction seen in the 65 to 74 and ≥ 75 years subgroups. Post hoc analyses of CFB in trough FEV1 and proportion of SGRQ responders at week 52 were significantly greater with FF/UMEC/VI than with FF/VI or UMEC/VI in all subgroups. No new safety signals were identified. Interpretation: FF/UMEC/VI reduced the rate of moderate/severe exacerbations and improved lung function and health status vs FF/VI and UMEC/VI irrespective of age for most end points, with a similar safety profile. Clinical Trial Registration: ClinicalTrials.gov; No.: NCT02164513; URL: www.clinicaltrials.govCTT116855
AB - Background: In the Informing the Pathway of COPD Treatment (IMPACT) trial, single-inhaler triple-therapy fluticasone furoate (FF), umeclidinium (UMEC), and vilanterol (VI) reduced moderate/severe exacerbation rates vs FF/VI and UMEC/VI in patients with symptomatic COPD and a history of exacerbations, with a similar safety profile. Research Question: Are trial outcomes with single-inhaler triple-therapy FF/UMEC/VI vs FF/VI and UMEC/VI affected by age in patients with symptomatic COPD and a history of exacerbations? Study Design and Methods: IMPACT was a phase III, double-blind, 52-week trial. Patients ≥ 40 years of age with symptomatic COPD and ≥ 1 moderate/severe exacerbation in the previous year were randomly assigned 2:2:1 to FF/UMEC/VI 100/62.5/25 μg, FF/VI 100/25 μg, or UMEC/VI 62.5/25 μg. End points assessed by age included annual rate of moderate/severe exacerbations, change from baseline (CFB) in trough FEV1, proportion of St. George's Respiratory Questionnaire (SGRQ) responders (≥ 4 units decrease from baseline in SGRQ total score), and safety. Results: The intention-to-treat population comprised 10,355 patients; 4,724 (46%), 4,225 (41%), and 1,406 (14%) were ≤ 64, 65 to 74, and ≥ 75 years of age, respectively. FF/UMEC/VI reduced on-treatment moderate/severe exacerbation rates vs FF/VI (% reduction [95% CI]: ≤ 64 years, 8% [−1 to 16]; P = .070; 65-74 years, 22% [14-29]; P < .001; ≥ 75 years, 18% [3-31]; P = .021) and vs UMEC/VI (≤ 64 years, 16% [7-25]; P = .002; 65-74 years, 33% [25-41]; P < .001; ≥ 75 years, 24% [6-38]; P = .012), with greatest rate reduction seen in the 65 to 74 and ≥ 75 years subgroups. Post hoc analyses of CFB in trough FEV1 and proportion of SGRQ responders at week 52 were significantly greater with FF/UMEC/VI than with FF/VI or UMEC/VI in all subgroups. No new safety signals were identified. Interpretation: FF/UMEC/VI reduced the rate of moderate/severe exacerbations and improved lung function and health status vs FF/VI and UMEC/VI irrespective of age for most end points, with a similar safety profile. Clinical Trial Registration: ClinicalTrials.gov; No.: NCT02164513; URL: www.clinicaltrials.govCTT116855
KW - COPD
KW - aging
KW - exacerbations
KW - safety
KW - single-inhaler triple therapy
UR - http://www.scopus.com/inward/record.url?scp=85101286979&partnerID=8YFLogxK
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U2 - 10.1016/j.chest.2020.09.253
DO - 10.1016/j.chest.2020.09.253
M3 - Article
C2 - 33031829
AN - SCOPUS:85101286979
SN - 0012-3692
VL - 159
SP - 985
EP - 995
JO - CHEST
JF - CHEST
IS - 3
ER -