title: Once-daily fluticasone furoate/vilanterol versus twice daily combination therapies in asthma-mixed treatment comparisons of clinical efficacy.
abstract: BACKGROUND
  Fluticasone furoate (FF)/vilanterol (VI) is a once-daily inhaled corticosteroid (ICS)/long-acting beta2agonist (LABA) combination. FF/VI, 92/22mcg and 184/22mcg, are approved in Europe as maintenance therapy in persistent asthma. We report data from mixed treatment comparisons (MTC) of once-daily FF/VI against established twice-daily ICS/LABA combination therapies on clinical efficacy outcomes.
  
  
  METHODS
  Data from 31 parallel-group randomised controlled trials (RCTs) of ICS/LABA, of ≥8 weeks' duration in patients aged ≥12 years with asthma, identified by systematic review, were analysed using covariate-adjusted Bayesian hierarchical models for four efficacy outcomes (primary analysis). Lung function, assessed by change from baseline morning peak expiratory flow (PEF) (n= 18 studies) and forced expiratory volume in 1 s (FEV1) (n= 28), was the outcome of primary interest. Secondary objectives were assessment of relative efficacy in terms of exacerbation rates (n= 6) and health status (n= 7). Overall, 24 different treatment arms were included in the MTC; we report findings comparing FF/VI (92/22mcg and 184/22mcg) with fluticasone propionate/salmeterol (FP/SAL) (250/50mcg and 500/50mcg) and budesonide/formoterol (BUD/FORM) (320/9mcg and 640/18mcg).
  
  
  RESULTS
  For PEF (margin = 12 l/min), FF/VI 92/22mcg demonstrated ≥94 % probability and FF/VI 184/22mcg >99 % probability of non-inferiority to corresponding doses of both FP/SAL and BUD/FORM. For FEV1(margin = 100 ml), FF/VI demonstrated ≥98 % (92/22mcg) and >99 % (184/22mcg) probability of non-inferiority to both FP/SAL and BUD/FORM. Findings for exacerbations were inconclusive due to lack of data: FF/VI 92/22mcg demonstrated 74 % and 82 % probability of non-inferiority (margin = 10 %) to FP/SAL 250/50mcg and BUD/FORM 320/9mcg, respectively. For Asthma Quality of Life Questionnaire (AQLQ) score, FF/VI 92/22mcg demonstrated >99 % and 90 % probability of non-inferiority (margin = 0.25) to FP/SAL 250/50mcg and BUD/FORM 320/9mcg. Data were unavailable to assess non-inferiority of FF/VI 184/22mcg on exacerbations or AQLQ.
  
  
  CONCLUSIONS
  Both strengths of once-daily FF/VI in asthma were comparable with corresponding doses of twice-daily FP/SAL and BUD/FORM in terms of lung function in this MTC analysis. FF/VI 92/22mcg was comparable with FP/SAL and BUD/FORM on AQLQ, but exacerbation results were inconclusive. Model limitations include disconnected treatment networks and variability across studies. Our data support previous RCT findings suggesting that the efficacy of once-daily FF/VI in improving lung function and health status in asthma is comparable with twice-daily ICS/LABAs.
authors.affiliation: Value Evidence and Outcomes, GlaxoSmithKline, Stockley Park West, Blg 10, 1-3 Iron Bridge Road, Uxbridge, Middlesex UB11 1BT UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Svedsater
authors.affiliation: Value Evidence and Outcomes, GlaxoSmithKline, Stockley Park West, Blg 10, 1-3 Iron Bridge Road, Uxbridge, Middlesex UB11 1BT UK.
authors.forename: Gillian
authors.initials: G
authors.lastname: Stynes
authors.affiliation: Value Evidence and Outcomes, GlaxoSmithKline, Stockley Park West, Blg 10, 1-3 Iron Bridge Road, Uxbridge, Middlesex UB11 1BT UK.
authors.forename: Jaro
authors.initials: J
authors.lastname: Wex
authors.affiliation: Respiratory Medicines Development Centre, GlaxoSmithKline, Stockley Park, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Frith
authors.affiliation: Respiratory Medicines Development Centre, GlaxoSmithKline, Stockley Park, UK.
authors.forename: David
authors.initials: D
authors.lastname: Leather
authors.affiliation: Health Investment Evidence (Formerly), Global Health Outcomes, GlaxoSmithKline, Stockley Park, UK.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Castelnuovo
authors.affiliation: Berry Consultants LLC, Austin, TX USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Detry
authors.affiliation: Berry Consultants LLC, Austin, TX USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Berry
keywords: Asthma; Fluticasone furoate; ICS/LABA; Mixed treatment comparison; Network meta-analysis; Vilanterol