Ciclesonide, a novel inhaled steroid, does not affect hypothalamic-pituitary-adrenal axis function in patients with moderate-to-severe persistent asthma.
BACKGROUND
Inhaled corticosteroids (ICSs) reduce local airway inflammation, which is an underlying cause of asthma symptoms. However, potential systemic side effects associated with ICS use are a major concern for asthmatic patients.


METHODS
Adult patients (n = 60; > or = 18 years of age) with moderate-to-severe asthma were randomized to receive 4 weeks of treatment with ciclesonide (CIC), 320 microg bid (CIC 640), CIC, 640 microg bid (CIC 1280), fluticasone propionate (FP), 440 microg bid (FP 880), FP 880 microg bid (FP 1760), or placebo (PBO) [all doses expressed as ex-actuator; comparable to ex-valve doses of 800 and 1,600 microg/d for CIC and 1,000 and 2,000 microg/d for FP, respectively].


RESULTS
After 29 days of treatment, CIC 640, CIC 1280, and FP 880 had no significant effect on the mean serum cortisol area under the curve for 0 to 24 h (AUC0-24h). FP 1760 produced a statistically significant suppression in mean serum cortisol AUC0-24h compared to PBO (p = 0.0009; 95% confidence interval [CI] -117.5 [corrected] to -32.1). Results obtained with cosyntropin stimulation revealed no statistically significant differences among the groups. The CIC 640 group demonstrated a significant increase compared to the PBO group in 24-h urinary cortisol levels from baseline at week 4 (p = 0.0224; 95% CI, 0.0023 to 0.0283), while the other treatment groups revealed no change in this parameter. The incidence of treatment-emergent adverse events was similar in all groups, and all adverse events were mild or moderate in severity.


CONCLUSIONS
Treatment with moderate and high doses of CIC does not result in hypothalamic-pituitary-adrenal-axis suppression as compared with PBO.
Szefler
Stanley
S
National Jewish Medical & Research Center, 1400 Jackson St, Room J313, Denver, CO 80206, USA. szeflers@njc.org
Rohatagi
Shashank
S
Williams
James
J
Lloyd
Mark
M
Kundu
Sudeep
S
Banerji
Donald
D
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy*; D003366:Cosyntropin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D000068298:Fluticasone; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011282:Pregnenediones / Q000008:administration & dosage*
D000305:Adrenal Cortex Hormones; D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D006728:Hormones; D011282:Pregnenediones; D003366:Cosyntropin; D000068298:Fluticasone; C120481:ciclesonide; D006854:Hydrocortisone