Combination Therapy with the Single Inhaler Salmeterol/Fluticasone Propionate versus Increased Doses of Inhaled Corticosteroids in Patients with Asthma

Although results from a few meta-analyses were most uniformly supportive of the beneficial effect of combination therapy on lung function, there were inconsistent results on other endpoints such as asthma exacerbation. Single inhalers of salmeterol and fluticasone propionate have been available, and some studies compared the effect of combination products with increased doses of inhaled corticosteroids (ICSs) on several outcome variables.We reviewed the studies systematically, providing a quantitative summary estimate on the efficacy and safety measures of the combination products.We searched databases (Medline and Embase) from January 1997 to December 2005 using 'fluticasone and salmerterol' or 'Seretide' or 'Advair', in combination with 'randomized controlled trial'. The databases of GlaxoSmithKline Clinical Trial Register and Cochrane Controlled Trials Register, or relevant articles were searched for additional studies.Combination products had a comparatively low, but significant improvement in pulmonary function, with morning peak expiratory flow (PEF), evening PEF and FEV1 increasing by 17.86 liters/min, 15.57 liters/min and 0.09 liter, respectively, compared with increased doses of inhaled corticosteroid (ICSs) over 12 weeks' treatment. But there were no statistically significant differences in other endpoints such as asthma exacerbation, overall withdrawal and drug-related adverse events, with the exception of overall adverse events and symptom free 24 h, which favored combination products.Thecombination products provided a statistically significant improvement in lung function and in symptoms but provided no significantly increased protection against exacerbation. Unless high doses of ICSs are required, there is insufficient evidence at present to recommend the use of combination products rather than increased moderate doses of ICSs as a first-line treatment for patients uncontrolled on their current doses of ICSs.