ORIGINAL ARTICLE

Systematic review of the dose-response relation of inhaled fluticasone propionate

M Masoli¹, M Weatherall², S Holt³, R Beasley¹

¹ Medical Research Institute of New Zealand, Wellington, New Zealand
² Wellington School of Medicine & Health Sciences, Wellington, New Zealand
³ P3 Research, Wellington, New Zealand

Correspondence to:
Correspondence to:
Professor R Beasley
Medical Research Institute of New Zealand, PO Box 10055, Wellington, New Zealand; richard.beasley{at}mrinz.ac.nz

Aims: To examine the dose-response relation of inhaled fluticasone for both efficacy and adrenal function in children with asthma.

Methods: Systematic review of double blind randomised dose-response studies of fluticasone in children of at least 4 weeks duration. Main outcome measures: FEV₁, morning peak expiratory flow, night awakenings, ß agonist use, major exacerbations, 12 or 24 hour urinary cortisol, peak plasma cortisol post-stimulation.

Results: Seven studies of 1733 children with asthma met the inclusion criteria for efficacy. The dose-response curve for each efficacy outcome measure suggested that the response began to plateau between 100 and 200 µg per day with additional efficacy at the 400 µg per day dose shown in one study of severe asthmatics. Five studies of 1096 children with asthma met the inclusion criteria for assessment of adrenal function. The largest placebo controlled study of 437 children reported no difference in 24 hour urinary cortisol between placebo and fluticasone at doses of 100 and 200 µg per day. The non-placebo controlled study of 528 children reported significant suppression of overnight urinary cortisol levels with fluticasone at 400 compared with 200 µg per day.

Conclusions: There is insufficient data to determine the dose-response of fluticasone in children at doses >400 µg per day. The dose-response curve for fluticasone appears to plateau between 100 and 200 µg per day for efficacy. There was additional efficacy at the 400 µg per day dose in children with severe asthma; however there was evidence of adrenal suppression at this dose.

Keywords: asthma; fluticasone; efficacy; adrenal function

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