The role of mepolizumab in atopic and nonatopic severe asthma with persistent eosinophilia

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To the Editor: Atopy is a common finding in asthma, but at least one third of severe asthmatics have no evidence of atopy (so-called “intrinsic” asthma) [1]–[4]. Despite the uncertainty of the mechanisms leading to nonatopic asthma, these patients have no history of allergic respiratory disease, no detectable specific IgE to common aeroallergens, and no positive skin-prick test. One hypothesis suggests that differences in the phenotypes might be driven by the local, and not by the systemic, production of IgE [5]. Eosinophils are involved in diverse inflammatory responses irrespective of atopy. Eosinophilic inflammation and IgE production are promoted by T-helper cell (Th)2 cytokines, such as interleukin (IL)-5, IL-4 and IL-13. IL-4/IL-13 are major factors involved in Th2 differentiation and IgE class switching [6], while IL-5 is involved primarily in eosinophil growth, survival, activation, and in mediating inflammation. Recurrent asthma exacerbations are a major problem in some patients and can predominate in a subgroup of asthmatics with elevated eosinophils, irrespective of their atopic status [2], [7]. Mepolizumab, a humanised monoclonal antibody against IL-5, selectively inhibits eosinophilic airway inflammation and has been shown to be associated with a significant reduction in severe asthma exacerbations irrespective of the baseline IgE levels or radioallergosorbent test (RAST) status in the Dose Ranging Efficacy And safety with Mepolizumab in severe asthma (DREAM) trial [7]. In this post hoc analysis of the DREAM trial, we aimed to: examine and discuss the effect of treatment with mepolizumab on the frequency of exacerbations in the atopic and nonatopic subgroups; to present the analyses of seasonal patterns of response by subgroup; and to evaluate changes in lung function and exhaled nitric oxide fraction ( F eNO) according to subgroup. Specific details …