Blood eosinophil dose response to oral corticosteroids in a population of patients with severe asthma

Introduction: Blood eosinophil count is a determinant of disease severity and anti-IL5 treatment response in patients with Severe Asthma. Use of oral corticosteroids (OCS) suppresses blood eosinophils in the presence of concomitant inhaled corticosteroids (ICS). There is, however, no published dose response for the extent of additional suppression by OCS in this population. Objectives: Evaluate the effect of OCS dose on blood eosinophil count in a population of patients with Severe Eosinophilic Asthma taking high dose ICS therapy. Methods: Baseline blood eosinophil count from two GSK-funded mepolizumab studies (DREAM, MENSA) was analysed post-hoc using linear and non-linear models for the relationship to maintenance OCS dose with adjustment for multiple covariates (study, region, weight, and past exacerbation history). Model predictions were corroborated using independent data from a third GSK-funded OCS-sparing Phase 3 study, SIRIUS. Results: In these studies, 28% of patients were taking maintenance OCS (median 10mg, IQR 7-20mg), there was a dose-ordered reduction of blood eosinophil count with increasing OCS dose group (prednisolone-equivalent dose >0-8, >8-16, >16-32 and >32mg): respective ratios 1.05, 0.68, 0.63 and 0.77 compared with no OCS. Analysis using a dose response (Emax) model suggested maximal inhibition of 44% and half maximal OCS dose of 12mg. An observed increase in blood eosinophil count of 33% for placebo patients in study SIRIUS corroborated model predictions. Conclusions: In patients with Severe Eosinophilic Asthma, OCS use on background maximum ICS therapy leads to additional dose-dependent reduction of blood eosinophils.