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.
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.
Authors: W W Busse; S Brazinsky; K Jacobson; W Stricker; K Schmitt; J Vanden Burgt; D Donnell; S Hannon; G L Colice Journal: J Allergy Clin Immunol Date: 1999-12 Impact factor: 10.793
Authors: J H Toogood; N M Lefcoe; D S Haines; B Jennings; N Errington; L Baksh; L Chuang Journal: J Allergy Clin Immunol Date: 1977-04 Impact factor: 10.793
Authors: P Chervinsky; A van As; E A Bronsky; R Dockhorn; M Noonan; C LaForce; W Pleskow Journal: J Allergy Clin Immunol Date: 1994-10 Impact factor: 10.793
Authors: D B Price; D Hernandez; P Magyar; J Fiterman; K M Beeh; I G James; S Konstantopoulos; R Rojas; J A van Noord; M Pons; L Gilles; J A Leff Journal: Thorax Date: 2003-03 Impact factor: 9.139