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Inhaled fluticasone propionate and adrenal effects in adult asthma: systematic review and meta-analysis

¹ Medical Research Institute of New Zealand, ² Wellington School of Medicine & Health Sciences, and ³ P3 Research, Wellington, New Zealand. ⁴ School of Medicine, University of Southampton, Southampton, UK.

CORRESPONDENCE: R. Beasley, Medical Research Institute of New Zealand, PO Box 10055, Wellington, New Zealand. Fax: 64 44729224. E-mail: Richard.Beasley{at}mrinz.ac.nz

Keywords: Adrenal suppression, asthma, dose–response, fluticasone, meta-analysis

Received: October 11, 2005
Accepted May 20, 2006

The dose–response relationship of inhaled fluticasone propionate (FP) for adrenal suppression in adults with asthma is not clear.

The current authors carried out a systematic review and meta-analysis of placebo-controlled randomised dose–response studies of 4 weeks’ duration, which assessed the adrenal effects of FP by cosyntropin stimulation tests in adult asthma. The main outcome measure was the proportion of subjects with adrenal function below the lower limit of the normal range.

Five studies, with a total of 732 subjects with asthma, met the inclusion criteria. Data on daily doses >1,000 µg were limited to one study. The proportion of subjects with adrenal function below the lower limit of the normal range on placebo was 3.9%; for a 500-µg per day increase in FP dose the odds of an abnormality increased by 1.38 (95% confidence interval 1.01–1.59). The continuous secondary outcome measures showed an inverse linear relationship with the FP dose up to 2,000 µg·day^-1.

In conclusion, for routine prescribing within the established therapeutic dose–response range (50–500 µg·day^-1), fluticasone propionate has minimal effects on adrenal function. This conclusion is limited by the paucity of long-term studies of daily doses of fluticasone propionate >1,000 µg and by the considerable individual variability in the response.