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. 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 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 the 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 data, without meta-analysis, indicated that 80% of the benefit at 1000 mug/day was achieved at doses of 70-170 mug/day and 90% by 100-250 mug/day. A quadratic meta-regression showed that the maximum achievable efficacy was obtained 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 difference in FEV, for an inhaled dose of 200 mug/day against higher doses showed 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 therapeutic benefit of inhaled fluticasone is achieved with a total daily dose of 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 individual patients and by the paucity of dose-response studies that included doses of > 500 mug/day.