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Meta-Analysis
. 2001 Aug 4;323(7307):253-6.
doi: 10.1136/bmj.323.7307.253.

Dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma: meta-analysis

S Holt  1 , A Suder, M Weatherall, S Cheng, P Shirtcliffe, R Beasley
Affiliations
Meta-Analysis

Dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma: meta-analysis

S Holt et al. BMJ. .

Abstract

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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Figures

Figure 1
Figure 1
Process of inclusion of studies in the meta-analysis
Figure 2
Figure 2
Odds ratio of remaining in a trial at a dose of 200 μg/day of fluticasone, compared with higher doses, in the five trials that compared a dose of 200 μg/day with higher doses (higher ratio=favours lower dose)
Figure 3
Figure 3
Standardised difference in FEV1 for the four studies that compared 200 μg/day fluticasone with higher doses (higher value=favours higher dose)
See this image and copyright information in PMC

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