Efficacy of aclidinium/formoterol 400/12 µg, analyzed by airflow obstruction severity, age, sex, and exacerbation history: pooled analysis of ACLIFORM and AUGMENT
Received 29 August 2018
Accepted for publication 8 January 2019
Published 26 February 2019 Volume 2019:14 Pages 479—491
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Charles Downs
Peer reviewer comments 2
Editor who approved publication: Dr Richard Russell
Anthony D D’Urzo,1 Dave Singh,2 James F Donohue,3 Edward M Kerwin,4 Anna Ribera,5 Eduard Molins,5 Ferran Chuecos,5 Diana Jarreta,5 Esther Garcia Gil5
1Department of Family and Community Medicine, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; 2Medicines Evaluation Unit, Manchester University NHS Foundation Trust, Manchester, UK; 3Division of Pulmonary Diseases & Critical Care Medicine, University of North Carolina School of Medicine at Chapel Hill, Chapel Hill, NC, USA; 4Clinical Research Institute of Southern Oregon, Medford, OR, USA; 5AstraZeneca, Barcelona, Spain
Background: Aclidinium/formoterol 400/12 µg is a twice-daily maintenance bronchodilator for COPD. This post hoc study evaluated aclidinium/formoterol vs aclidinium 400 µg, formoterol 12 µg, or placebo in patient subgroups.
Patients and methods: Data were pooled from two 24-week Phase III clinical trials (ACLIFORM and AUGMENT). Patients (N=3,394) were analyzed by baseline airflow obstruction severity (moderate/severe), age (<65/≥65 years), sex, and exacerbation history (0/≥1 exacerbation in the previous 12 months). Changes from baseline vs placebo and monotherapies were evaluated: morning pre-dose (trough) and morning 1-hour post-dose FEV1, Transition Dyspnea Index (TDI), and moderate/severe exacerbation rates (healthcare resource utilization [HCRU] and EXAcerbations of Chronic pulmonary disease Tool [EXACT] criteria).
Results: Aclidinium/formoterol improved the post-dose FEV1 vs placebo and monotherapy in all subgroups (all P<0.01) and trough FEV1 vs placebo (P<0.001) and formoterol (P<0.05) across all subgroups. Improvements in trough FEV1 were observed vs aclidinium in patients with severe airflow obstruction, patients aged <65 years, males, and patients with exacerbation history (P<0.05). Improvements in TDI were observed vs placebo in all subgroups (all P<0.001), monotherapies for patients with moderate (formoterol P<0.05) or severe airflow obstruction (aclidinium P<0.05), patients aged <65 years (aclidinium P<0.01, formoterol P<0.05), males (formoterol P<0.05), and patients with no exacerbation history (formoterol P<0.05). HCRU exacerbation rates were lower for aclidinium/formoterol vs placebo in patients with no exacerbation history (P<0.01). EXACT exacerbation rates were lower for aclidinium/ formoterol in patients with moderate airflow obstruction vs placebo and aclidinium, patients aged <65 years vs placebo and ≥65 years vs formoterol, males vs placebo, and patients with no exacerbation history vs placebo (all P<0.05).
Conclusion: Aclidinium/formoterol significantly improved post-dose FEV1, trough FEV1, and TDI vs placebo across all subgroups and vs monotherapy in many subgroups. These findings further support the benefits of aclidinium/formoterol for all patients with COPD.
Keywords: COPD, aclidinium, formoterol
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]