Background and objective: Combined therapy with inhaled corticosteroids (ICSs) and long-acting β₂-adrenoceptor agonists (LABAs) is the recommended approach for the treatment of patients with asthma that is uncontrolled on ICSs alone. Additional studies are needed to assess the safety and efficacy of combination treatment with ICSs and LABAs in patients with mild asthma. The aim of this study was to compare the efficacy and tolerability of once-daily salmeterol/ fluticasone propionate combination (SFC) with once-daily fluticasone propionate (FP) over a 12-week treatment period in patients with mild persistent asthma.

Methods: This was a randomized, double-blind, placebo-controlled, parallel-group, multicentre study carried out in primary care or at a hospital outpatient department and included patients 12–79 years of age with mild persistent asthma (n = 458). After a 2-week run-in period, patients were randomized to receive SFC 50 μg/100 μg (n = 149), FP 100 μg (n = 154) or placebo (n = 155) once daily in the morning for 12 weeks. The primary efficacy endpoint was patient-recorded pre-dose mean morning peak expiratory flow (PEF). Other assessments included asthma symptom scores, use of rescue medication and investigator-recorded exacerbations. Lung function was measured and assessed during clinic visits.

Results: For the primary efficacy endpoint of mean change in morning PEF, SFC achieved significantly greater increases from baseline than both placebo (difference in adjusted means 23 L/min; 95% CI 15.0, 30.3; p < 0.001) and FP (difference in adjusted means 14 L/min; 95% CI 6.3, 21.7; p < 0.001). Compared with those who received FP, patients in the SFC group demonstrated significantly greater improvements in mean evening PEF (95% CI 11.7, 28.1; p < 0.001), forced expiratory volume in 1 second (95% CI 0.093, 0.257; p < 0.001), forced expiratory flow between 25% and 75% of forced vital capacity (95% CI 0.242, 0.617; p < 0.001), the percentage of symptom-free days (95% CI 0.34, 0.87; p = 0.011), and the percentage of rescue medication-free days (95% CI 0.34, 0.90; p = 0.018). During weeks 5–12, 52% of patients in the SFC group achieved ‘well controlled’ asthma, compared with 42% and 26% of patients in the FP and placebo groups, respectively. Only one patient (receiving placebo) had a severe asthma exacerbation during the study; the frequency of adverse events was similar across the three treatment groups.

Conclusion: Once-daily SFC 50 μg/100 μg provided significantly greater improvements in lung function and in asthma symptoms than once-daily FP 100 μg alone in patients with mild persistent asthma. However, twice-daily treatment with either SFC or ICSs plus short acting β₂-adrenoceptor agonists could be required to achieve guideline-defined asthma control in some patients.