Once-daily fluticasone furoate (FF)/vilanterol reduces risk of severe exacerbations in asthma versus FF alone

Eric D Bateman, Paul M O'Byrne, William W Busse, Jan Lötvall, Eugene R Bleecker, Leslie Andersen, Loretta Jacques, Lucy Frith, Jessica Lim, Ashley Woodcock, Eric D Bateman, Paul M O'Byrne, William W Busse, Jan Lötvall, Eugene R Bleecker, Leslie Andersen, Loretta Jacques, Lucy Frith, Jessica Lim, Ashley Woodcock

Abstract

Background: Combination therapy with an inhaled corticosteroid (ICS) and long-acting β2 agonist (LABA) is recommended for patients with asthma symptomatic on ICS alone. However, there is ongoing debate regarding the risk-benefit ratio of using LABA in asthma.

Objective: To evaluate the effect of the addition of a novel LABA, vilanterol (VI), to a once-daily ICS, fluticasone furoate (FF), on the risk of severe asthma exacerbations in patients with uncontrolled asthma.

Methods: This randomised double-blind comparative study of variable duration (≥ 24-78 weeks) was designed to finish after 330 events (each patient's first on-treatment severe asthma exacerbation). 2019 patients with asthma aged ≥ 12 years with ≥ 1 recorded exacerbation within 1 year were randomised and received FF/VI 100/25 μg or FF 100 μg, administered once daily in the evening. The primary endpoint was time to first severe exacerbation; secondary endpoints were rate of severe asthma exacerbations per patient per year and change in trough evening forced expiratory volume in 1 s (FEV1) from baseline.

Results: Compared with FF, FF/VI delayed the time to first severe exacerbation (HR 0.795, 95% CI 0.642 to 0.985) and reduced the annualised rate of severe exacerbations (rate reduction 25%, 95% CI 5% to 40%). Significantly greater improvements in trough FEV1 (p<0.001) were observed with FF/VI than with FF at weeks 12, 36, 52 and at endpoint. Both treatments were well tolerated with similar rates of treatment-related adverse events and on-treatment serious adverse events.

Conclusions: Once-daily FF/VI reduced the risk of severe asthma exacerbations and improved lung function compared with FF alone, with good tolerability and safety profile in adolescents and adults with asthma currently receiving ICS.

Clinicaltrialsgov no: NCT01086384.

Keywords: Asthma; Asthma Pharmacology.

Figures

Figure 1
Figure 1
Patient disposition and reasons for withdrawal post-screening. *One patient was not randomised but received FF 100 μg in error and one patient was randomised but did not receive treatment; these patients are not included in the ITT population. The patient who received FF 100 μg in error received 5 days of treatment and then was withdrawn. No safety issues were identified during this treatment period; FF, fluticasone furoate; ITT, intent-to-treat; SAE, severe adverse event; VI, vilanterol.
Figure 2
Figure 2
Cox proportional hazards model cumulative incidence curve for time to first severe asthma exacerbation, intent-to-treat population. FF, fluticasone furoate; VI, vilanterol.
Figure 3
Figure 3
Adjusted mean changes from baseline in trough forced expiratory volume in 1 s (L), intent-to-treat population. *Treatment differences p

Figure 4

Mean self-reported daily rescue use…

Figure 4

Mean self-reported daily rescue use (albuterol/salbutamol) 14 days before and after the onset…

Figure 4
Mean self-reported daily rescue use (albuterol/salbutamol) 14 days before and after the onset of severe asthma exacerbation for patients who experienced ≥1 or 0 severe asthma exacerbations, intent-to-treat population. *Date of onset was determined by the investigator and recorded in their clinical notes. For patients who experienced ≥1 severe asthma exacerbation, all severe asthma exacerbations are included in the figure. Rescue use in patients who did not exacerbate during the study was calculated for the same duration (number of days) as each exacerbation event in exacerbating patients. For this purpose, the surrogate Day 0 for non-exacerbators was the median study day of onset for all exacerbations. FF, fluticasone furoate; VI, vilanterol.
Figure 4
Figure 4
Mean self-reported daily rescue use (albuterol/salbutamol) 14 days before and after the onset of severe asthma exacerbation for patients who experienced ≥1 or 0 severe asthma exacerbations, intent-to-treat population. *Date of onset was determined by the investigator and recorded in their clinical notes. For patients who experienced ≥1 severe asthma exacerbation, all severe asthma exacerbations are included in the figure. Rescue use in patients who did not exacerbate during the study was calculated for the same duration (number of days) as each exacerbation event in exacerbating patients. For this purpose, the surrogate Day 0 for non-exacerbators was the median study day of onset for all exacerbations. FF, fluticasone furoate; VI, vilanterol.

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