Enhanced synergy between fluticasone propionate and salmeterol inhaled from a single inhaler versus separate inhalers

Background: The coadministration of long-acting inhaled beta(2)-agonists and inhaled corticosteroids is the most effective treatment for persistent asthma. Objective: This meta-analysis aimed to determine the efficacy of fluticasone propionate and salmeterol inhaled from a single inhaler (combination therapy) or from separate inhalers (concurrent therapy). Methods: Four similarly designed double-blind studies individually confirmed equivalence between combination and concurrent therapy on the basis of the primary efficacy measure (morning peak expiratory flow [PEF]). Each study showed a consistent trend in favor of combination therapy. Individual patient data from these studies were combined to provide overall estimates of treatment effect for morning PEF and other efficacy measures. Results: Fixed-effects meta-analysis showed a significant advantage for combination therapy compared with concurrent therapy in morning PEF (mean difference between groups in change from baseline over 12 weeks of 5.4 L/min; P = .006; 95% CI = 1.5-9.2). Logistic regression analysis showed that the odds of achieving a greater than 15 or greater than 30 L/min improvement with combination therapy were increased by approximately 40% compared with those after concurrent therapy (15 L/min: odds ratio = 1.42, P = .008, 95% CI = 1.1-1.8; 30 L/min: odds ratio = 1.40, P = .006, 95% CI = 1.1-1.8), representing an additional 7% to 9% and 5% to 14% more patients, respectively, on combination therapy responding compared with those on concurrent therapy. Conclusion: The meta-analysis indicates that the fluticasone propionate plus salmeterol combination offers the potential for increased clinical efficacy over concurrent use of the same doses of the same 2 drugs. After administration from a single inhaler, fluticasone propionate and salmeterol might codeposit in the airways. It is hypothesized that this codeposition offers an increased opportunity for synergistic interaction to occur.