Effect of ciclesonide and fluticasone on hypothalamic-pituitary-adrenal axis function in adults with mild-to-moderate persistent asthma.
BACKGROUND
Despite their proven efficacy in the treatment and prevention of asthma exacerbations, current inhaled corticosteroids carry safety concerns, especially adrenal suppression. Ciclesonide (hydrofluoroalkane propellant) is a novel inhaled corticosteroid with few, if any, clinical adverse events.


OBJECTIVE
To evaluate the potential effects of ciclesonide therapy on the dynamic cortisol response to sequential low- and high-dose cosyntropin stimulation in adults with mild-to-moderate persistent asthma.


METHODS
This was a double-blind, randomized, placebo-controlled, 12-week study in adults with mild-to-moderate asthma. One hundred sixty-four patients were randomized and treated; 148 patients completed the study. Fluticasone propionate (chlorofluorocarbon propellant) was used as an active comparator. The doses administered were 320 microg of ciclesonide once daily, 320 microg of ciclesonide twice daily, and 440 microg of fluticasone propionate twice daily, all doses ex-actuator.


RESULTS
For both ciclesonide groups, changes in mean low- and high-dose peak serum cortisol levels and in 24-hour urinary free cortisol levels corrected for creatinine were small vs baseline and comparable with placebo. For the fluticasone propionate group, significant reductions vs placebo in serum cortisol levels in response to high-dose cosyntropin stimulation and in 24-hour urinary free cortisol levels were observed. Oral candidiasis rates were 2.5% for 320-microg/d ciclesonide, 2.4% for 640-microg/d ciclesonide, and 22.0% for 880-microg/d fluticasone propionate.


CONCLUSIONS
These findings confirm the safety of ciclesonide therapy, demonstrating that at doses up to 640 microg/d, the drug does not affect sensitive markers of adrenal function.
Lipworth
Brian J
BJ
Allergy Research Group, Department of Medicine and Therapeutics, University of Dundee, Dundee, Scotland. b.j.lipworth@dundee.ac.uk
Kaliner
Michael A
MA
LaForce
Craig F
CF
Baker
James W
JW
Kaiser
Harold B
HB
Amin
Dilip
D
Kundu
Sudeep
S
Williams
James E
JE
Engelstaetter
Renate
R
Banerji
Donald D
DD
D000293:Adolescent; D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000009:adverse effects / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D003366:Cosyntropin / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D000068298:Fluticasone; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000503:physiopathology; D011282:Pregnenediones / Q000009:adverse effects / Q000627:therapeutic use*
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D011282:Pregnenediones; D003366:Cosyntropin; D000068298:Fluticasone; C120481:ciclesonide; D006854:Hydrocortisone