Dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma: meta-analysis
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S Holt1, A Suder, M Weatherall
1Wellington Asthma Research Group, Wellington School of Medicine, PO Box 7343, Wellington, New Zealand.
Objective:
To examine the dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma.
Design:
Meta-analysis of placebo controlled, randomised clinical trials that presented data on at least one outcome measure of asthma and that used at least two different doses of fluticasone.
Setting:
Medline, Embase, and GlaxoWellcome's internal clinical study registers.
Main Outcome Measures:
FEV(1), morning and evening peak expiratory flow, night awakenings, beta agonist use, and major exacerbations.
Results:
Eight studies, with 2324 adolescents and adults with asthma, met the inclusion criteria. Data on doses of >500 microg/day were limited. The dose-response curve for the raw data began to reach a plateau at around 100-200 microg/day and peaked by 500 microg/day. A negative exponential model for the data, without meta-analysis, indicated that 80% of the benefit at 1000 microg/day was achieved at doses of 70-170 microg/day and 90% by 100-250 microg/day. A quadratic meta-regression showed that the maximum achievable efficacy was obtained by doses of around 500 microg/day. The odds ratio for patients remaining in a study at a dose of 200 microg/day, compared with higher doses, was 0.73 (95% confidence interval 0.49 to 1.08). Comparison of the standardised difference in FEV(1 )for an inhaled dose of 200 microg/day against higher doses showed a difference in FEV(1) of 0.13 of a standard deviation (-0.02 to 0.29).
Conclusions:
In adolescent and adult patients with asthma, most of the therapeutic benefit of inhaled fluticasone is achieved with a total daily dose of 100-250 microg, and the maximum effect is achieved with a dose of around 500 microg/day. However, these findings were limited by the lack of data on individual patients and by the paucity of dose-response studies that included doses of >500 microg/day.
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