End‐point selection to determine the airway‐systemic ratio of inhaled corticosteroids in asthma

Abstract

Key PointsThe use of adenosine monophosphate challenge and basal cortisol as short‐term surrogate end points of airway‐systemic effects of inhaled corticosteroids in asthma is not suitable to properly determine the clinically relevant long‐term therapeutic index.

Inhaled Corticosteroids in Subjects with Chronic Obstructive Pulmonary Disease: An Old, Unfinished History

“…The efficacy of fluticasone propionate and fluticasone furoate is dependent on the intact molecule, and these two molecules should be considered as distinct. ICS marketed for use in COPD exhibits a range of potency, physicochemical properties, and pharmacokinetic parameters, as displayed in Table 2 [78][79][80][81][82][83]. Notably, the effect of a certain ICS may be modulated by the concomitant use of long-acting bron-chodilator(s) [84,85], even if the clinical relevance of this interaction has not yet been fully established.…”

“…However, this result has been criticized. Lipworth et al [82] noted that there was no evident separation in bronchoprotection between different doses of ICSs, and the respective confidence intervals were overlapping. Moreover, the test challenge was possibly biased, being organized at 12 h post dose for all ICS when only fluticasone furoate, which is administered once daily, resulted fully effective.…”

“…Moreover, the test challenge was possibly biased, being organized at 12 h post dose for all ICS when only fluticasone furoate, which is administered once daily, resulted fully effective. In addition, the duration of dosing for this arm was only 1 week, which is too short a period to establish any clinically meaningful degree of HPA suppression, favoring ICSs with higher lipophilicity [82]. Other authors [83] dispute that long retention in the airways is necessarily advantageous for ICS molecules.…”