S. Holt et al., Dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma: meta-analysis, BR MED J, 323(7307), 2001, pp. 253
Citations number
27
Categorie Soggetti
General & Internal Medicine","Medical Research General Topics
Objective To examine the dose-response relation of inhaled fluticasone prop
ionate 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 regist
ers.
Main outcome measures FEV1, 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 th
e inclusion criteria. Data on doses of > 500 mug/day were limited. The dose
-response curve for the raw data began to reach a plateau at around 100-200
mug/day and peaked by 500 mug/day. A negative exponential model for the da
ta, without meta-analysis, indicated that 80% of the benefit at 1000 mug/da
y was achieved at doses of 70-170 mug/day and 90% by 100-250 mug/day. A qua
dratic meta-regression showed that the maximum achievable efficacy was obta
ined by doses of around 500 mug/day. The odds ratio for patients remaining
in a study at a dose of 200 mug/day, compared with higher doses, was 0.73 (
95% confidence interval 0.49 to 1.08). Comparison of the standardised diffe
rence in FEV, for an inhaled dose of 200 mug/day against higher doses showe
d a difference in FEV1 of 0.13 of a standard deviation (-0.02 to 0.29).
Conclusions In adolescent and adult patients with asthma, most of the thera
peutic benefit of inhaled fluticasone is achieved with a total daily dose o
f 100-250 mug, and the maximum effect is achieved with a dose of around 500
mug/day. However, these findings were limited by the lack of data on indiv
idual patients and by the paucity of dose-response studies that included do
ses of > 500 mug/day.