Efficacy and safety profile of fluticasone/formoterol combination therapy compared to its individual components administered concurrently in asthma: a randomised controlled trial

BACKGROUND: The potent inhaled corticosteroid, fluticasone propionate (fluticasone), and the long-acting β2-agonist with a rapid onset of action, formoterol fumarate (formoterol), have now been combined in a single aerosol inhaler, fluticasone/formoterol (flutiform). This study investigated the efficacy and safety of fluticasone/formoterol combination therapy compared with its individual components administered concurrently via two separate inhalers. METHODS: Patients ≥ 12 years (N = 210) with mild to moderate-severe persistent, reversible asthma were evenly randomised to 12 weeks of treatment (b.i.d.) with fluticasone/formoterol combination therapy (100/10 μg b.i.d. or 250/10 μg b.i.d.) or fluticasone plus formoterol (Flixotide Evohaler, pMDI, Flovent [HFA]; Foradil, DPI, Foradil Aerolizer) administered concurrently (fluticasone + formoterol; 100 μg + 12 μg b.i.d. or 250 μg + 12 μg b.i.d.) in an open-label, parallel-group, multicentre study. The primary objective of this study was to show non-inferiority of fluticasone/formoterol compared with fluticasone + formoterol based on mean post-dose FEV1. RESULTS: The mean FEV1 30-60 minutes post-dose on Day 84 was approximately 2.6 L in both the fluticasone/formoterol combination and the fluticasone + formoterol treatment groups (per protocol sets; treatment difference least squares (LS) mean: -0.03 L; 95% CI: -0.148, 0.081). The lower limit of the 95% CI (-0.148 L) was above the non-inferiority threshold of ≥-0.2 L. Analyses of other pulmonary function tests, patient reported outcomes, rescue medication use, asthma exacerbations and quality of life questionnaires were also comparable. The safety profiles of the two study groups were similar overall. TRIAL REGISTRATION: Fluticasone/formoterol combination therapy had comparable efficacy to its individual components administered concurrently, when measured by post-dose FEV1 in patients aged ≥ 12 years with mild to moderate-severe asthma. The safety and tolerability profile of fluticasone/formoterol combination therapy was similar to that of its individual components administered concurrently. Although this was an open-label study, the results remain compelling: the primary efficacy measure was a physical endpoint and study statisticians were blinded to treatment allocations until analysis was completed.