Whether the combination of a once-daily inhaled corticosteroid with a once-daily longacting beta-2 agonist is more protective than a once-daily longacting beta-2 agonist alone against exacerbations of chronic obstructive pulmonary disease ( COPD ) is unknown.
Researchers hypothesised that Fluticasone furoate and Vilanterol ( Breo Ellipta; Relvar Ellipta ) would prevent more exacerbations than would Vilanterol alone.
Two replicate double-blind parallel-group 1 year trials were made. Both studies began on Sept 25, 2009. Study 1 ended on Oct 31, 2011, and study 2 on Oct 17, 2011.
Eligible patients were aged 40 years or older, had a history of COPD, a smoking history of 10 or more pack-years, a ratio of forced expiratory volume in 1 s ( FEV1 ) to forced vital capacity of 0.70 or less after bronchodilators ( and an FEV1 of 70% or less of predicted ), and a documented history of one or more moderate or severe disease exacerbations in the year before screening.
Patients were randomly assigned ( 1:1:1:1 ) on the basis of the Registration and Medication Ordering System to 25 mcg Vilanterol alone or 25 mcg Vilanterol combined with either 50 mcg, 100 mcg, or 200 mcg Fluticasone furoate once daily.
The primary endpoint was the yearly rate of moderate and severe exacerbations. The trials were analysed separately and a pooled analysis was also done.
1622 patients in study 1 and 1633 patients in study 2 were randomly assigned.
In study 1, no significant difference in exacerbation rate was noted between the 200/25 mcg Fluticasone furoate / Vilanterol group and the Vilanterol only group ( mean 0.90 events vs 1.05 events per year; ratio 0.9 ). Because of the statistical hierarchy used, researchers could not infer significance for the 50 mcg and 100 mcg groups.
In study 2, significantly fewer moderate and severe exacerbations were noted in all Fluticasone furoate / Vilanterol groups than in the Vilanterol only group ( p=0.0398 for the 50 mcg group, 0.0244 for the 100 mcg group, and 0.0004 for the 200 mcg group ). In the pooled analysis, significantly fewer moderate and severe exacerbations were noted in all Fluticasone furoate / Vilanterol groups than in the Vilanterol only group ( 0.0141 for the 50 mcg group, p less than 0.0001 for the 100 mcg group, and 0.0003 for the 200 mcg group ).
Nasopharyngitis was the most frequently reported adverse event in both studies. Pneumonia and fractures were reported more frequently with Fluticasone furoate and Vilanterol than with Vilanterol alone.
Eight deaths from pneumonia were noted in the Fluticasone furoate / Vilanterol groups compared with none in the Vilanterol only group.
Addition of Fluticasone furoate to Vilanterol was associated with a decreased rate of moderate and severe exacerbations of COPD in patients with a history of exacerbation, but was also associated with an increased pneumonia risk. ( Xagena )
Dransfield MT et al, The Lancet Respiratory Medicine 2013; 1: 210-223