OBJECTIVES: To determine the relative treatment efficacy of FF/VI, a once-daily inhaled corticosteroid (ICS)/long-acting beta agonist (LABA) combination therapy, compared with corresponding dosages of established twice-daily ICS/LABA therapies, in patients with asthma. METHODS: Following a systematic literature review, data from 31 parallel-group randomized controlled trials, consisting of 24 different treatments, of >8 weeks’ duration and in patients aged ≥12 years were included in the mixed treatment comparison. Bayesian hierarchical models were used to investigate four endpoints: lung function (peak expiratory flow [PEF] (n=18 studies) and forced expiratory volume in one second [FEV] (n=28)), annual exacerbation rates (n=6), and health status (Asthma Quality of Life Questionnaire [AQLQ]) (n=7). We compared ICS/LABA dosages licensed in Europe, and report findings from comparisons of once-daily FF/VI (92/22mcg and 184/22mcg) with twice-daily fluticasone propionate (FP)/salmeterol (SAL) (250/50mcg and 500/50mcg) and budesonide (BUD)/formoterol (FORM) (400/12mcg and 800/24mcg). RESULTS: On PEF, based on a 12L/min delta, FF/VI 92/22mcg and 184/22mcg demonstrated ≥94% and >99% probability of non-inferiority to corresponding doses of FP/SAL and BUD/FORM, respectively. On FEV, based on a 100mL threshold, FF/VI demonstrated ≥99% and ≥98% probability of non-inferiority to FP/SAL and BUD/FORM. On exacerbations, using a 10% event rate ratio delta, FF/VI 92/22mcg demonstrated 74% and 82% probability of non-inferiority to corresponding doses of FP/SAL and BUD/FORM. On AQLQ, based on a score delta of 0.25, FF/VI 92/22mcg demonstrated >99% and 90% probability of non-inferiority to FP/SAL and BUD/FORM. There were insufficient data to assess non-inferiority of FF/VI 184/22mcg on exacerbations or AQLQ. CONCLUSIONS: Our findings suggest that once-daily FF/VI has comparable efficacy with established twice-daily combination therapies in asthma. Key limitations include weak/disconnected treatment networks and susceptibility of the results to study inclusion criteria. FUNDING: GlaxoSmithKline (HO-12-10140)