Effects of budesonide by means of the Turbuhaler on the hypothalmic-pituitary-adrenal axis in asthmatic subjects: a dose-response study.

Abstract

As a general phenomenon, corticosteroids may suppress the activity in the hypothalamic-pituitary-adrenal (HPA) axis. The adrenal stimulation test is a commonly used method to assess the relative risk of exogenous corticosteroids to induce systemic side effects. This clinical trial was performed to assess the effects of budesonide on the HPA axis (at 800, 1600, or 3200 microg/day, given as a twice daily regimen, administered by means of the Turbuhaler) in adult patients with mild, non-steroid-dependent asthma. Sixty-four asthmatic patients received budesonide or placebo by inhalation or 10 mg/day oral prednisone once daily as a positive control in a double-blind, double-dummy, randomized, placebo-controlled, parallel-group, multicenter study. Plasma cortisol concentration was measured to assess the effect on the HPA axis before and during a 6-hour infusion of synthetic adrenocorticotropic hormone (ACTH), cosyntropin. After 6 weeks of treatment, plasma cortisol concentrations after adrenal stimulation by cosyntropin infusion had fallen by 4% in the placebo group; by 13%, 11%, and 27% in the budesonide groups (800, 1600, and 3200 microg/day, respectively); and by 35% in the prednisone group. The decrease was significant only in the 3200 microg/day budesonide (p = 0.03) and prednisone (p = 0.005) groups. Over the same time period, decreases in basal plasma cortisol concentrations were 1% in the placebo group; 19%, 19%, and 34% in the three budesonide groups; and 37% in the prednisone group. Only in the prednisone group was the decrease significant (p = 0.03 vs placebo). In this study budesonide inhaled by means of the Turbuhaler, at doses recommended for clinical use (800 or 1600 microg/day), did not produce any statistically significant suppression of the HPA axis compared with placebo.