Incruse Ellipta: New once-daily inhaled antimuscarinic for COPD

1 December 2014

Incruse Ellipta (umeclidinium) is a once-daily long-acting anticholinergic bronchodilator used to relieve symptoms of chronic obstructive pulmonary disease (COPD) in adults

NICE recommends adding a LAMA to a regimen containing an inhaled long-acting beta agonist and a corticosteroid in patients who remain breathless or have exacerbations despite their existing treatment.

PHARMACOLOGY

Umeclidinium bromide is a long-acting muscarinic receptor antagonist (LAMA) which causes bronchodilation by inhibiting the binding of acetylcholine to muscarinic cholinergic receptors on smooth muscle in the airways.¹

CLINICAL STUDIES

The efficacy of once-daily umeclidinium (administered via the Ellipta inhaler) was evaluated in two double-blind, placebo-controlled phase III trials involving 904 adults with COPD: a 12-week study and a 24-week study.^2,3

Lung function

In both studies, statistically significant and clinically meaningful improvements in lung function, defined by change from baseline trough FEV₁ (primary endpoint) at study end, were observed for umeclidinium compared with placebo (least squares mean treatment difference +127ml in the 12-week study and +115ml in the 24-week study; p<0.001 for both). The bronchodilatory effects of umeclidinium were evident from the first day of treatment and did not attenuate over time.^2,3

Umeclidinium was associated with a greater weighted mean improvement from baseline in FEV₁ over 0–6 hours post-dose than placebo at study end in both the 12-week study (166ml, p<0.001) and the 24-week study (150ml, p<0.001).^2,3

Breathlessness

Investigators observed a significant improvement in transition dyspnoea index focal score at week 24 with umeclidinium compared with placebo in the longer study (p<0.001) but statistical significance was not reached at week 12 in the shorter study.^2,3

Quality of life

Improvements in quality of life were also observed for umeclidinium. Patients treated with umeclidinium had a statistically significant reduction in St. George’s Respiratory Questionnaire total score compared with placebo in both studies (p<0.001).^2,3

COPD exacerbations

At week 24, the probability of experiencing a COPD exacerbation was 8.9% in patients treated with umeclidinium compared with 13.7% in those receiving placebo (HR 0.6, p=0.035).³

Rescue medication

The 12-week study showed a significant reduction from baseline in use of rescue medication (salbutamol) in the umeclidinium group compared with the placebo group, with a mean reduction of 0.7 puffs per day (p=0.025). In both the 12- and 24-week studies, patients receiving umeclidinium had a higher percentage of days when no rescue medication was needed (46.3% vs 35.2% and 31.1% vs 21.7%, respectively) although no formal statistical testing was performed on this endpoint.¹