SELECTED ARTICLES FROM THE RECENT LITERATURE 2005

11/7/05

Comparison of ciclesonide and fluticasone effects on the HPA axis

Summary
Background - Ciclesonide (Cic) is a new, unique inhaled corticosteroid (ICS) pro-drug converted in the lower airways to an active metabolite. Fluticasone propionate (FP) is an extensively used ICS with very high affinity for corticosteroid receptors.

Findings - Szefler et al of the national Jewish Medical and Research Center in Denver, CO compared varying b.i.d. doses of Cic and FP with placebo for 4 weeks in 60 adults with moderate to severe asthma.

On the 29th day, the found no effects on HPA function (as indicated by the area under the curve for sequential serum cortisol levels) of Cic 640, Cic 1280 and FP 880 microg/day when compared to placebo treatment . However, there was a significant suppression of the cortisol levels in those treated with FP 1760 microg/day (p=0.0009). There were no significant differences in the findings in cosyntropin stimulation tests in those receiving the different treatments.

Adverse effects observed were mild and did not vary in frequency among the different treatment groups.

Reference
Chest 2005;128:1104-14

Editor's Comments
The authors concluded that Cic up to at least 1280 microg/day had no effect on HPA. Their findings also suggest that FP 1760 microg/day (but not 880 microg/day) did suppress HPA function although the HPA reserve was retained (normal cosyntropin test). These findings differ somewhat from that reported recently by Lipworth et al who found that treatment with FP 880 microg/day suppressed HPA function (Chest 2005;1104:1104-14). This difference could be due to the longer duration of treatment (12 weeks) in the study by Lipworth et al. This longer duration of treatment is more relevant to the "real world" ICS treatment of moderate to severe asthma.

It is understandable why sizable doses of Cic do not suppress HPA function. Almost all the Cic metabolite which is absorbed systemically from the lungs is almost completely bound to plasma proteins and thereby not available in free form to bind to corticosteroids receptors on systemic tissues.

 

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