Abstract
BackgroundPatients with asthma uncontrolled on inhaled corticosteroids may benefit from umeclidinium (UMEC), a long-acting muscarinic antagonist.MethodsThis Phase IIb, double-blind study included patients with reversible, uncontrolled/partially-controlled asthma for ≥6 months, receiving ≥100 mcg/day fluticasone propionate (or equivalent) for ≥12 weeks. Following a 2-week run-in on open-label fluticasone furoate (FF) 100 mcg, patients were randomised (1:1:1) to receive UMEC 31.25 mcg, UMEC 62.5 mcg or placebo on top of FF 100 mcg once-daily for 24 weeks. As-needed salbutamol was provided. Primary and secondary endpoints were change from baseline in clinic trough forced expiratory volume in 1 s (FEV1) and clinic FEV1 3 h post-dose, respectively, at Week 24. Other endpoints included change from baseline in home daily spirometry (trough FEV1, evening FEV1, morning [pre-dose] and evening peak expiratory flow) over 24 weeks. Safety was assessed throughout the study.ResultsThe intent-to-treat population comprised 421 patients (UMEC 31.25 mcg: n =139, UMEC 62.5 mcg: n =139, placebo: n =143). UMEC 31.25 mcg and 62.5 mcg demonstrated significantly greater improvements from baseline in clinic trough FEV1 at Week 24 (difference [95% CI]: 0.176 L [0.092, 0.260; p<0.001] and 0.184 L [0.101, 0.268; p<0.001], respectively), clinic FEV1 3 h post-dose at Week 24 (0.190 L [0.100, 0.279; p<0.001] and 0.198 L [0.109, 0.287; p<0.001], respectively) and mean change from baseline in daily home spirometry over 24 weeks versus placebo. No new safety signals were identified.ConclusionsUMEC is a highly effective bronchodilator that leads to improved lung function when administered as a single bronchodilator on top of FF in subjects with fully reversible, uncontrolled/partially-controlled moderate asthma. These data support a favourable benefit/risk profile for UMEC (31.25 mcg and 62.5 mcg).Trial registrationGSK study ID: 205832; Clinicaltrials.gov ID: NCT03012061.
Highlights
Patients with asthma uncontrolled on inhaled corticosteroids may benefit from umeclidinium (UMEC), a long-acting muscarinic antagonist
Asthma is associated with respiratory symptoms and variable airflow limitation, and patients can be prone to exacerbations that may require treatment with systemic corticosteroids, urgent care visits or hospitalisations [2]
While an Minimal clinically important difference (MCID) in forced expiratory volume in 1 s (FEV1) has not been formally defined in asthma, a previous Phase III study of patients with persistent asthma showed that fluticasone furoate (FF) 100 mcg and FF/VI 100/25 mcg improved trough FEV1 by 136 mL and 172 mL, respectively, compared with placebo [25]
Summary
Patients with asthma uncontrolled on inhaled corticosteroids may benefit from umeclidinium (UMEC), a long-acting muscarinic antagonist. Asthma is associated with respiratory symptoms and variable airflow limitation, and patients can be prone to exacerbations that may require treatment with systemic corticosteroids, urgent care visits or hospitalisations [2]. The Global Initiative for Asthma (GINA) 2019 strategy report recommends inhaled corticosteroids (ICS) as a controller treatment for patients with asthma [2]. Despite the availability of ICS treatment, which is often associated with improvements in symptom control, lung function and number of exacerbations [2], many patients remain uncontrolled; in 2010, 53.5% of treated patients with asthma in European countries were assessed as having not well-controlled asthma by the Asthma Control Test (trademark of QualityMetric Incorporated) [5]
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