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.


CONCLUSIONS
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.
Nelson
Harold S
HS
National Jewish Medical and Research Center, Denver, CO 80206, USA.
Chapman
Kenneth R
KR
Pyke
Stephen D
SD
Johnson
Malcolm
M
Pritchard
John N
JN
D000280:Administration, Inhalation; D000420:Albuterol / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000730:Androstadienes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D000068298:Fluticasone; D006801:Humans; D008168:Lung / Q000503:physiopathology; D009330:Nebulizers and Vaporizers; D000068299:Salmeterol Xinafoate
D000730:Androstadienes; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol