Prevention of clinically important deteriorations in COPD with umeclidinium/vilanterol
Authors Singh D, Maleki-Yazdi MR, Tombs L, Iqbal A, Fahy WA, Naya I
Received 1 December 2015
Accepted for publication 19 February 2016
Published 24 June 2016 Volume 2016:11(1) Pages 1413—1424
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 3
Editor who approved publication: Dr Richard Russell
Dave Singh,1 M Reza Maleki-Yazdi,2 Lee Tombs,3 Ahmar Iqbal,4 William A Fahy,5 Ian Naya5
1Medicines Evaluation Unit, University of Manchester, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK; 2Division of Respiratory Medicine, Women’s College Hospital, University of Toronto, ON, Canada; 3Precise Approach LTD, London UK; 4Respiratory Medical Franchise, GSK, Research Triangle Park, NC, USA; 5Respiratory Medicines Development Centre, GSK, Stockley Park, Middlesex, UK
Background: Minimizing the risk of disease progression and exacerbations is the key goal of COPD management, as these are well-established indicators of poor COPD prognosis. We developed a novel composite end point assessing three important aspects (lung function, health status, and exacerbations) of worsening in COPD. The objective was to determine whether dual bronchodilation with umeclidinium/vilanterol (UMEC/VI) reduces clinically important deteriorations (CIDs) in COPD versus placebo or bronchodilator monotherapy.
Methods: This study is a post hoc analysis of two 24-week trials comparing UMEC/VI 62.5/25 µg with UMEC 62.5 µg, VI 25 µg, or placebo (Study A; NCT01313650), or UMEC/VI 62.5/25 µg with tiotropium (TIO) 18 µg (Study B; NCT01777334) in patients with symptomatic COPD, without a history of frequent exacerbations. Deterioration was assessed as the time to a first CID, a composite measure defined as a decrease of ≥100 mL in trough forced expiratory volume in 1 second or ≥4-unit increase in St George’s Respiratory Questionnaire total score or an on-treatment moderate-to-severe COPD exacerbation.
Results: In Study A, fewer patients experienced a first CID with UMEC/VI (44%) versus UMEC (50%), VI (56%), and placebo (75%). The risk of a first CID was reduced with UMEC/VI (hazard ratio [HR]: 0.37 [95% confidence interval, CI: 0.30, 0.45]), UMEC (HR: 0.46 [95% CI: 0.38, 0.56]), and VI (HR: 0.55 [95% CI: 0.45, 0.66]; all P<0.001) versus placebo, and with UMEC/VI versus UMEC (HR: 0.80 [95% CI: 0.65, 0.97]; P<0.05) and versus VI (HR: 0.67 [95% CI: 0.55, 0.81]; P<0.001). In Study B, fewer patients experienced a first CID with UMEC/VI (41%) versus TIO (59%). UMEC/VI reduced the risk of a first composite CID by 43% versus TIO (HR: 0.57 [95% CI: 0.47, 0.69]; P<0.001).
Conclusion: This exploratory analysis, using a new assessment of clinical deterioration in COPD, revealed that a majority of symptomatic patients with low exacerbation risk experienced a deterioration during the 24-week study periods. UMEC/VI reduces the risk of a first CID versus placebo or bronchodilator monotherapy.
Keywords: COPD, deterioration, airway stability, UMEC/VI
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