Comparable effects of inhaled fluticasone propionate and budesonide on the HPA-axis in adult asthmatic patients

Abstract

This randomized, double-blind, double-dummy, multicentre cross-over study compared the effects on the hypothalamic-pituitary-adrenal (HPA) axis of fluticasone propionate (750 μ g twice daily given via the DiskusTMand budesonide (800 μ g twice daily given via the TurbuhalerTM. Two treatment periods of 2 weeks each were preceded by a 2-week run-in period and separated by a 2-week washout period. During run-in and washout, patients received beclomethasone dipropionate (BDP) or budesonide at a constant dose of 1500–1600 μ g day−1. Sixty patients aged 18–75 years with moderate to severe asthma not fully controlled by treatment with 1500–1600 μ g day−1budesonide or BDP entered run-in and 45 completed the study. HPA axis suppression was assessed by morning serum cortisol (area under the curve from 08·00 to 10·30 hours) and 12-h nocturnal urinary cortisol excretion, measured at the end of run-in (baseline 1), at the end of washout (baseline 2), and at the end of each treatment period.Neither budesonide nor fluticasone produced significant suppression of either parameter compared to baselines. Only a few patients had serum-cortisol and urinary cortisol values below the normal range, before and after treatment. This shows that the patients did not have adrenal suppression before entering the study. The ratio between the AUC serum cortisol measured after fluticasone treatment and after budesonide treatment was 0·99 (95% CI 0·92–1·06), indicating equivalent effects on the HPA axis. This result was achieved after having omitted two patients' results, due to their very sensitive reaction to budesonide, but not to fluticasone. Two exacerbations of acute asthma occurred during budesonide treatment and none during fluticasone treatment. Both treatments were well tolerated. In conclusion, budesonide 1600 μ g day−1via TurbuhalerTMand fluticasone propionate 1500μ g day−1via DiskusTMhad no clinical effects on the HPA axis in patients with moderate to severe asthma.