Dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma: meta-analysis.
OBJECTIVE
To examine the dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma.


METHODS
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.


METHODS
Medline, Embase, and GlaxoWellcome's internal clinical study registers.


METHODS
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.
Holt
S
S
Wellington Asthma Research Group, Wellington School of Medicine, PO Box 7343, Wellington, New Zealand.
Suder
A
A
Weatherall
M
M
Cheng
S
S
Shirtcliffe
P
P
Beasley
R
R
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology; D001507:Beclomethasone / Q000008:administration & dosage; D019819:Budesonide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D000068298:Fluticasone; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D008297:Male; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D019819:Budesonide; D000068298:Fluticasone; D001507:Beclomethasone