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

Ciclesonide Reduces the Need for Oral Steroid Use in Adult Patients With Severe, Persistent AsthmaInhaled corticosteroids (ICS) are the most effective agents for controlling persistent asthma. However, in very severe cases and during exacerbations, oral corticosteroids (OCS) are necessary. As systemic adverse events (AEs) are associated with OCS use, oral steroid-sparing strategies are employed and have been demonstrated with ICS such as be-clomethasone dipropionate, budesonide, and fluticasone propionate in patients with moderate-to-severe asthma. However, ICS administered in high doses for prolonged periods are associated with AEs such as hoarseness, moniliasis, and the suppression of hypothalamic-pituitary-adrenal (HPA)-axis function. Consequently, the ideal ICS is one that is OCS sparing but has minimal AEs. comments
Ciclesonide is a novel ICS currently under development for the treatment of persistent asthma, Inactive in its parent form, and with a weak affinity for glucocorticoid receptors, ciclesonide is converted to its active metabolite, desisobutyryl-ciclesonide (des-CIC), by esterases, primarily in the lungs. Studies suggest that ciclesonide may provide a high level of efficacy against the symptoms of asthma, comparable with that of available ICS, including budesonide and fluticasone propionate.” Ciclesonide reduces airway hyperresponsiveness to adenosine-5′-monophosphate,’ methacholine, and allergen challenge, and improves pulmonary function in patients with asthma.
In addition, ciclesonide has a favorable safety profile and does not affect the circadian rhythm of serum cortisol, suggesting it has no clinically relevant effect on HPA-axis function. Importantly, des-CIC has a rapid clearance rate and a high degree of serum protein binding, potentially leading to low systemic exposure. Furthermore, low rates of oral candidiasis and other local oropharyngeal effects have been observed, presumably as a result of the low oropharyngeal deposition of ciclesonide, which is approximately half that of budesonide and fluticasone propionate, and the even lower oral deposition of des-CIC, which is 25-fold lower than that of active budesonide, and one tenth that of active fluticasone propionate. In addition, ciclesonide demonstrates limited oral conversion to des-CIC.

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