Ciclesonide Reduces the Need for Oral Steroid Use in Adult Patients With Severe, Persistent Asthma: Summary

Criteria for selecting an ICS for OCS-sparing therapy must include improved safety, with respect to both systemic and local AEs. The safety profile of an ICS is influenced by many factors, including the degree of systemic bioavailability. Suppression of HPA-axis function and adrenal insufficiency are indicative of a higher degree of systemic bioavailabil-ity and are best assessed with measures such as the cosyntropin test, which reflects the capacity of the adrenal cortex response to physiologic stimulation. In our study, patients in all three treatment groups exhibited suppressed HPA-axis function at baseline, which was attributed to the use of OCS. Treatment with ciclesonide appeared to facilitate the recovery of normal HPA-axis function at the end of the study in a significant proportion of patients, as demonstrated by the increased peak serum cortisol levels after cosyntropin stimulation. This improvement in HPA-axis function may have been due to greater OCS reduction in the ciclesonide groups and the substitution of other forms of ICS with ciclesonide. These findings are consistent with results from other published ciclesonide studies in patients with asthma in which little, if any, suppression of cortisol levels was evident, even with high doses of ciclesonide. other

In contrast, a direct comparative study examining the effects of fluticasone propionate on HPA-axis function found that 9 days of treatment with fluticasone propionate, 500 (ex-valve), decreased plasma cortisol levels by 29% and the 24-h urinary cortisol profile by approximately 44%, while 1,000 ^g (ex-valve) reduced plasma cortisol levels by 59% and the 24-h urinary cortisol profile by 69%. The suppressed functioning of the HPA-axis seen at the beginning of the current study is a common effect associated with the longterm use of OCS. This effect, along with reduced bone growth in the young, is attributable to the endocrine activity of corticosteroids and is identical to the syndrome of endogenous corticosteroid excess (Cushing syndrome).

The therapeutic margin of ciclesonide may be attributed to its novel pharmacokinetic/pharmacodynamic properties, which include its low oral bioavail-ability, high serum protein binding, and rapid elimination. Importantly, ciclesonide is formulated as a solution for delivery via HFA-MDI, which results in high lung deposition. It is inactive until converted to des-CIC in the target tissues, which, together with its pharmacologic properties, contribute to its potentially improved therapeutic margin. Initial data indicate that ciclesonide demonstrates comparable efficacy with other ICS in patients with persistent asthma and, in addition, is associated with minimal local or systemic AEs.
In conclusion, the results of this study suggest that twice-daily treatment with inhaled ciclesonide (640 ^g/d or 1,280 ^g/d) is a well-tolerated method for reducing (and potentially discontinuing) OCS use in patients with severe, persistent asthma, thus minimizing the risk of the AEs associated with OCS use.