10/6/03 Enhanced synergy between fluticasone propionate and salmeterol inhaled from a single inhaler vs separate inhalersSummaryA number of recent studies have shown the benefit of adding treatment with inhaled salmeterol (SALM), a long acting beta agonist, to low dosage inhaled corticosteroids (ICS) therapy in the management of persistent asthma. Based on these findings, Advair, an MDI containing a combination of SALM and fluticasone propionate (FP), a widely used ICS, was approved for clinical use by the FDA. But is the use of this combination inhaler more effective than when the FP and SALM are used concurrently but from separate MDI? Nelson et al of the National Jewish Medical and Research Center in Denver, CO carried out a meta-analysis of 4 similarly designed double-blind studies comparing Combination (FP and SALM in one MDI) and Concurrent (FP and SALM in separate MDI) therapies in persistent asthma. Each study showed a consistent trend in favor the Combination therapy using morning peak flow rates (PEFR) as the primary endpoint. When data from all 4 studies were pooled a fixed effects meta-analysis showed greater improvement in PEFR following Combination therapy (p=0.006) with a 40% greater chance of achieving a 30L/min improvement in PEFR following Combination therapy. The authors postulated that co-deposition of FP and SALM in the airways following inhalation from the Combination MDI might provide an opportunity for synergistic interaction of the drugs and a resultant greater efficacy. Reference J Allergy Clin Immunol 2003; 112:29-36 Editor's Comments The combination of FP and SALM in the Advair product has been advantageous in being more convenient to use (than 2 separate inhalers) with an implied improved patient compliance with therapy. The findings described above suggest that inhaling FP and SALM at the exact same time might be more effective as well. However, the greater improvement in PEFR seen after 12 weeks of Combination therapy was not much more than after Concurrent therapy (mean=5.4L/min). The percentage of patients who exhibited a more impressive increase in PEFR (ä 30L/min) after the Combination therapy was only 5-14% more than seen after Concurrent therapy. We are not provided with data concerning changes in asthma symptom scores, full spirometry or Quality of Life measures. An inhaler with a combination of formoterol, another long acting beta agonist, and budesonide (Symbicort) is under extensive investigation at present. A recent report (Resp Med 2003; 97:702-8) described equal efficacy of the Symbicort and its 2 components inhaled concurrently but separately. However, there were fewer dropouts in the Symbicort treatment group.
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