High-dose inhaled steroids in asthmatics: moderate efficacy gain and suppression of the hypothalamic-pituitary-adrenal (HPA) axis. Research Council of the Norwegian Thoracic Society

Abstract

H Hi ig gh h--d do os se e i in nh ha al le ed d s st te er ro oi id ds s i in n a as st th hm ma at ti ic cs s:: m mo od de er ra at te e e ef ff fi ic ca ac cy y g ga ai in n a an nd d s su up pp pr re es ss si io on n o of f t th he e h hy yp po ot th ha al la am mi ic c--p pi it tu ui it ta ar ry y--a ad dr re en na al l ( (H HP PA A) ) a ax xi is s J. Boe*, P. Bakke**, T. Rødølen + , E. Skovlund ++ , A. Gulsvik**, The study was a randomized, double-blind, 3 month, multicentre study. One hundred and thirty four asthmatics currently using inhaled steroids (0.4-1.6 mg BDP or budesonide (BUD)) were stratified according to pretrial daily steroid use. Within each stratum they were randomized to either 1.6 mg BDP or 2.0 mg FP. A significant increase in the primary efficacy variables, i.e. mean morning and evening peak expiratory flow (PEF) (approximately 20 l·min -1 ) during the treatment period, was found for both treatments. No significant differences between the drugs were revealed for these primary or any other secondary efficacy variables (use of beta 2 -agonists, symptom scores, and PEF, forced vital capacity (FVC), forced expiratory volume in one second (FEV 1 ) recorded at the clinical visits). However, significant differences between treatments occurred regarding decrease of serum cortisol and adrenocorticotropic hormone.We conclude that, although both treatments gave statistically significant increases in efficacy parameters when compared with baseline, the increases were so small that they can be regarded as being clinically unimportant. Daily doses of BDP, 1.6 mg, and FP, 2.0 mg, had comparable effects on lung function. A suppression of the hypothalamic pituitary adrenal (HPA) axis was only found with a daily dose of 2 mg FP.

Systematic review and economic analysis of the comparative effectiveness of different inhaled corticosteroids and their usage with long-acting beta2 agonists for the treatment of chronic asthma in adults and children aged 12 years and over

“…Cross-over design, 1:2 dose ratio. In the study by Malo and colleagues, 210 there was no significant 205 only reported morning and evening PEF as estimated increases per day over the treatment period. Baseline and end-point values were also reported, but for morning and evening PEF combined.…”

“…Again, there were no significant differences between groups (no p-values presented). Boe and colleagues 205 did not report this outcome measure.…”

“…191,[204][205][206][207][208][209][210][211][212] The studies were predominantly parallel in design but three trials used cross-over designs. [210][211][212] The studies varied considerably in size (from 21 to 340 participants) and length (from 6 weeks to 2 years).…”

“…Boe and colleagues 205 randomised participants (stratified by their pretrial dose of ICS) to either 2000 µg of FP daily or 1600 µg of BDP daily for 3 months. The study drugs were delivered by Diskhaler DPI (Rotadisk, GSK -not explicitly stated but deduced from the text).…”

Adrenal suppression with chronic dosing of fluticasone propionate compared with budesonide in adult asthmatic patients

“…maintained throughout the 12 weeks of the Our results agree with those of Grahnen et al 8 evaluation. 12 Furthermore, after a further two who reported suppression of plasma cortisol weeks washout there was still detectable sup-(as AUC 0-20 ) of 28% when fluticasone was pression in the fluticasone group, suggesting given as a single dose of 1000 g via a Diskhaler prolonged body retention. Another factor to healthy volunteers compared with 65% when which may partially explain the observed it was given as 1000 g twice daily for three differences between the two drugs is that the and a half days.…”