Elsevier

Respiratory Medicine

Volume 112, March 2016, Pages 65-74
Respiratory Medicine

Magnitude of umeclidinium/vilanterol lung function effect depends on monotherapy responses: Results from two randomised controlled trials

https://doi.org/10.1016/j.rmed.2016.01.001Get rights and content
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Highlights

  • We identified COPD patients as either responders or non-responders to umeclidinium or vilanterol monotherapy.

  • Response was defined as an increase from baseline in forced expiratory volume in 1s (FEV1) of ≥12% and ≥200mL, on Day 1.

  • We found that both responders and non-responders achieved clinical benefit from dual treatment.

  • Long acting bronchodilator monotherapy responders and non-responders attain clinical benefit from dual therapy in COPD.

  • Non-responders to both monotherapies achieved a clinically meaningful lung function response which was more than additive.

Abstract

Purpose

Dual therapy with bronchodilators of different pharmacological classes may produce greater lung function improvements than either drug alone. However, the relationship between a patient's response to monotherapy and response to dual bronchodilator therapy is currently unknown. We aimed to investigate whether dual therapy with umeclidinium/vilanterol provides additional benefit over umeclidinium or vilanterol monotherapy in patients with chronic obstructive pulmonary disease (COPD) identified as responsive (increase from baseline in forced expiratory volume in 1s [FEV1] of ≥12% and ≥200 mL, Day 1) or non-responsive to monotherapy.

Methods

In two randomised, double-blind, three-way complete-block, cross-over studies (DB2116132 n = 207; DB2116133 n = 182; intent-to-treat), all patients (moderate-to-very severe COPD) were randomised to 1 of 6 sequences and received once-daily umeclidinium 62.5mcg, vilanterol 25mcg, and umeclidinium/vilanterol 62.5/25mcg (one treatment/14-day period; 10–14-day washout). Key endpoints were 0–6 h weighted mean FEV1 (Day 14) and trough FEV1 (Day 15). Adverse events, vital signs and COPD exacerbations were assessed. Pooled data are presented.

Results

Umeclidinium/vilanterol significantly (p ≤ 0.001, unless stated otherwise) increased 0–6 h weighted mean FEV1 versus umeclidinium in umeclidinium-responders (+114 mL), versus vilanterol in vilanterol-responders (+92 mL) and versus umeclidinium (+70 mL) and vilanterol (+62 mL) in non-responders. Improvements in trough FEV1 occurred with umeclidinium/vilanterol versus umeclidinium in umeclidinium-responders (+77 mL), versus vilanterol in vilanterol-responders (+86 mL), and versus umeclidinium (+42 mL [p = 0.020]) and vilanterol (+58 mL) in non-responders. All treatments were well tolerated.

Conclusions

Once-daily umeclidinium/vilanterol significantly improved lung function in patients with COPD, with quantitatively greater improvements in patients identified as responders to umeclidinium and vilanterol monotherapy than non-responders.

Keywords

COPD pharmacology
Chronic obstructive pulmonary disease
Bronchodilators

Abbreviations

AE
adverse event
ANCOVA
analysis of covariance
BMI
body mass index
CI
confidence interval
COPD
chronic obstructive pulmonary disease
ECG
electrocardiogram
FEV1
forced expiratory volume in 1 second
FVC
forced vital capacity
GOLD
Global initiative for chronic Obstructive Lung Disease
ITT
intent-to-treat
LS
least squares
LABA
long-acting beta2-agonist
LAMA
long-acting muscarinic antagonist
MCID
minimally clinically important difference
NA
not analysed
SD
standard deviation
SE
standard error
UMEC
umeclidinium
VI
vilanterol
wm
weighted mean

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