Once-daily fluticasone furoate alone or combined with vilanterol in persistent asthma

Paul M O'Byrne, Eugene R Bleecker, Eric D Bateman, William W Busse, Ashley Woodcock, Richard Forth, William T Toler, Loretta Jacques, Jan Lötvall, Paul M O'Byrne, Eugene R Bleecker, Eric D Bateman, William W Busse, Ashley Woodcock, Richard Forth, William T Toler, Loretta Jacques, Jan Lötvall

Abstract

The inhaled corticosteroid fluticasone furoate (FF) and the long-acting β₂ agonist vilanterol (VI) are in development as a combined once-daily therapy for asthma and chronic obstructive pulmonary disease. Our study objectives were to compare the efficacy and safety of once-daily FF/VI with FF alone and twice-daily fluticasone propionate (FP) in patients aged ≥12 years with moderate-to-severe persistent asthma. Patients (n=586) received FF/VI 200/25 μg or FF 200 μg once-daily (evening dosing), or FP 500 μg twice-daily for 24 weeks. Co-primary end-points were change from baseline in trough forced expiratory volume in 1 s (FEV₁) weighted mean (wm) 0-24 h serial FEV1. Secondary end-points included change from baseline in percentage of rescue-free 24-h periods, percentage of symptom-free 24-h periods and total Asthma Quality of Life Questionnaire (AQLQ). Safety assessments included adverse events, 24-h urinary cortisol excretion, vital signs and ECG. FF/VI significantly improved trough FEV1 and wmFEV₁ versus FF and FP. Significantly more rescue-free and symptom-free 24-h periods were reported with FF/VI versus FF. Treatment differences for AQLQ were not significant. Incidence of adverse events was similar across groups. No clinically significant differences were seen for 24-h urinary cortisol excretion, vital signs or ECG. FF/VI resulted in statistically greater improvements in lung function and symptomatic end-points versus FF, and was well tolerated in this asthma population.

Trial registration: ClinicalTrials.gov NCT01134042.

Conflict of interest statement

Conflict of interest: Disclosures can be found alongside the online version of this article at www.erj.ersjournals.com

Figures

Figure 1–
Figure 1–
Consort/patient flow diagram. FF: fluticasone furoate; FP: fluticasone propionate; ITT: intent-to-treat; VI: vilanterol. #: one patient was randomised to the FP 500 μg group in error, but did not receive study drug and was thus not included in the ITT population.
Figure 2–
Figure 2–
Repeated measures analysis for the primary end-point of change from baseline in trough forced expiratory volume in 1 s over 24 weeks of treatment (intent-to-treat population). Data are presented as least squares mean (95% CI). FF: fluticasone furoate; VI: vilanterol; FP: fluticasone propionate.
Figure 3–
Figure 3–
Adjusted mean change from baseline of individual serial forced expiratory volume in 1 s assessments following 24 weeks of treatment (intent-to-treat population). Data are presented as least squares mean (95% CI). FF: fluticasone furoate; VI: vilanterol; FP: fluticasone propionate.
Figure 4–
Figure 4–
Cumulative incidence curves for withdrawals due to lack of efficacy over the 24-week treatment period (intent-to-treat population). FF: fluticasone furoate; VI: vilanterol; FP: fluticasone propionate.

References

    1. British Thoracic Society and Scottish Intercollegiate Guidelines Network British guideline on the management of asthma: a national clinical guideline. Thorax 2008; 63: Suppl. 4, iv1–iv121
    1. Global Initiative for Asthma Global Strategy for Asthma Management and Prevention, 2012. Date last updated: December, 2012. Date last accessed: October 9, 2013
    1. Fanta CH. Drug therapy: asthma. N Engl J Med 2009; 360: 1002–1014
    1. Price D, Robertson A, Bullen K, et al. Improved adherence with once-daily versus twice-daily dosing of mometasone furoate administered via a dry powder inhaler: a randomized open-label study. BMC Pulm Med 2010; 10: 1.
    1. US prescribing information for veramyst (fluticasone furoate) nasal spray Indicated for treatment of symptoms of seasonal and perennial allergic rhinitis in adults and children ≥2 years. Date last updated: October, 2011. Date last accessed: October 9, 2013
    1. European Medicines Agency authorisation codes EU/1/07/434/001; EU/1/07/434/002; EU/1/07/434/003 Avamys (fluticasone furoate) indicated for the treatment of symptoms of allergic rhinitis: summary of product characteristics. Date last accessed: October 9, 2013
    1. Biggadike K, Bledsoe RK, Hassell AM, et al. X-ray crystal structure of the novel enhanced-affinity glucocorticoid agonist fluticasone furoate in the glucocorticoid receptor-ligand binding domain. J Med Chem 2008; 51: 3349–3352
    1. Salter M, Biggadike K, Matthews JL, et al. Pharmacological properties of the enhanced-affinity glucocorticoid fluticasone furoate in vitro and in an in vivo model of respiratory inflammatory disease. Am J Physiol Lung Cell Mol Physiol 2007; 293: 660–667
    1. Bateman ED, Bleecker ER, Lötvall J, et al. Dose effect of once-daily fluticasone furoate in persistent asthma: a randomized trial. Respir Med 2012; 106: 642–650
    1. Bleecker ER, Bateman ED, Busse WW, et al. Once-daily fluticasone furoate is efficacious in patients with symptomatic asthma on low-dose inhaled corticosteroids. Ann Allergy Asthma Immunol 2012; 109: 353–358
    1. Busse WW, Bleecker ER, Bateman ED, et al. Fluticasone furoate demonstrates efficacy in patients with asthma symptomatic on medium doses of inhaled corticosteroid therapy: an 8-week, randomised, placebo-controlled trial. Thorax 2012; 67: 35–41
    1. Woodcock A, Bleecker ER, Busse WW, et al. Fluticasone furoate: once-daily evening treatment versus twice-daily treatment in moderate asthma. Respir Res 2011; 12: 160.
    1. Ducharme FM, Ni Chroinin M, Greenstone I, et al. Addition of long-acting β2-agonists to inhaled corticosteroids versus same dose inhaled corticosteroids for chronic asthma in adults and children. Cochrane Database Syst Rev 2010; 5: CD005535.
    1. Lötvall J, Bateman ED, Bleecker ER, et al. 24 h duration of the novel LABA vilanterol trifenatate in asthma patients treated with ICSs. Eur Respir J 2012; 40: 570–579
    1. O’Byrne PM, Bleecker ER, Bateman ED, et al. Efficacy and safety of fluticasone furoate (FF)/vilanterol (VI) once daily (OD) for 24 weeks in persistent asthma. Eur Respir J 2012; 40: Suppl. 56, S313
    1. National Institutes for Health Guidelines for the Diagnosis and Management of Asthma (EPR-3). Date last updated: August, 2007. Date last accessed: October 9, 2013
    1. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. Date last updated: 2008. Date last accessed: October 9, 2013
    1. International Conference on Harmonisation Tripartite Guideline Guidance for Good Clinical Practice E6 (R1). 1996. Date last accessed: October 9, 2013
    1. Williams LK, Peterson EL, Wells K, et al. Quantifying the proportion of severe asthma exacerbations attributable to inhaled corticosteroid nonadherence. J Allergy Clin Immunol 2011; 128: 1185–1191
    1. Bender BG. Overcoming barriers to nonadherence in asthma treatment. J Allergy Clin Immunol 2002; 109: Suppl. 6, S554–S559
    1. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther 2001; 23: 1296–1310
    1. Ni Chroinin M, Greenstone I, Lasserson TJ, et al. Addition of inhaled long-acting β2-agonists to inhaled steroids as first line therapy for persistent asthma in steroid-naive adults and children. Cochrane Database Syst Rev 2009; 7: CD005307.
    1. Cloutier MM, Schatz M, Castro M, et al. Asthma outcomes: composite scores of asthma control. J Allergy Clin Immunol 2012; 129: S24–S33

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