Superiority of fluticasone propionate/formoterol fumarate versus fluticasone propionate alone in patients with moderate-to-severe asthma: a randomised controlled trial

OBJECTIVE: To demonstrate the efficacy and safety of fluticasone propionate/formoterol fumarate (flutiform) in a pressurised metered-dose inhaler (pMDI) compared to two formulations of the fluticasone propionate component (Skyepharma fluticasone [SKP FP] or Flovent, GlaxoSmithKline [GSK FP]) in adults and adolescents with moderate-to-severe asthma. METHODS: Patients included in the study were ≥12 years, with symptomatic asthma for ≥1 year, steroid-requiring, had a forced expiratory volume in the first second (FEV1) of 40% to 80% (inclusive) of predicted normal values, and documented reversibility within 12 months of the study. Albuterol/salbuterol was given as rescue medication. The primary efficacy endpoint was the change in FEV1 from morning pre-dose at baseline (week 0) to 2 hours post-dose at week 12 for fluticasone/formoterol compared to SKP FP and, additionally, compared to GSK FP. RESULTS: Fluticasone/formoterol was demonstrated to be statistically significantly superior to SKP FP. The least squares (LS) mean difference in FEV1 from baseline pre-dose to 2 hours post-dose at week 12 was 0.161 L (95% CI: 0.078, 0.245, p < 0.001). Fluticasone/formoterol also demonstrated superior efficacy against GSK FP (LS mean difference = 0.185 L, 95% CI: 0.102, 0.268, p < 0.001). Results from multiple secondary and tertiary efficacy endpoints assessing lung function, asthma symptoms, exacerbations and rescue medication use supported a superior efficacy of the fluticasone/formoterol combination over both fluticasone formulations. Treatment-emergent adverse events were lowest in the fluticasone/formoterol group (32.9%) compared to SKP FP (39.7%) or GSK FP (40.4%). CONCLUSIONS: Results from this study demonstrate that fluticasone/formoterol 250/10 µg b.i.d. provides superior efficacy compared to fluticasone alone for the management of moderate-to-severe asthma, with a safety profile similar to that of fluticasone monotherapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00649025; EudraCT number: 2007-005653-37.