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Background The use of anti-interleukin-5 (IL5) for severe asthma is based on criteria from randomised controlled trials (RCTs), but in real-life patients might not fulfil the eligibility criteria but may benefit from biologics. We aimed to characterise patients starting anti-IL5(R) in Europe and evaluate the discrepancies between initiation of anti-IL5(R) in real life and in RCTs. Materials and methods We performed a cross-sectional analysis with data from the severe asthma patients at the start of anti-IL5(R) in the Severe Heterogeneous Asthma Research collaboration Patient-centred (SHARP Central) registry. We compared the baseline characteristics of the patients starting anti-IL5(R) from 11 European countries within SHARP with the baseline characteristics of the severe asthma patients from 10 RCTs (four for mepolizumab, three for benralizumab and three for reslizumab). Patients were evaluated following eligibility criteria from the RCTs of anti-IL5 therapies. Results Patients starting anti-IL5(R) in Europe (n=1231) differed in terms of smoking history, clinical characteristics and medication use. The characteristics of severe asthma patients in the SHARP registry differed from the characteristics of patients in RCTs. Only 327 (26.56%) patients fulfilled eligibility criteria of all the RCTs; 24 patients were eligible for mepolizumab, 100 for benralizumab and 52 reslizumab. The main characteristics of ineligibility were: ≥10 pack-years, respiratory diseases other than asthma, Asthma Control Questionnaire score ≤1.5 and low-dose inhaled corticosteroids. Conclusion A large proportion of patients in the SHARP registry would not have been eligible for anti-IL5(R) treatment in RCTs, demonstrating the importance of real-life cohorts in describing the efficacy of biologics in a broader population of patients with severe asthma.

Abstract There is wide variability in the response to inhaled corticosteroids (ICS) in asthma. While some of this heterogeneity of response is due to adherence and environmental causes, genetic variation also influences response to treatment and genetic markers may help guide treatment. Over the past years, researchers have investigated the relationship between a large number of genetic variations and response to ICS by performing pharmacogenomic studies. In this systematic review we will provide a summary of recent pharmacogenomic studies on ICS and discuss the latest insight into the potential functional role of identified genetic variants. To date, seven genome wide association studies (GWAS) examining ICS response have been published. There is little overlap between identified variants and methodologies vary largely. However, in vitro and/or in silico analyses provide additional evidence that genes discovered in these GWAS (e.g. GLCCI1, FBXL7, T gene, ALLC, CMTR1) might play a direct or indirect role in asthma/treatment response pathways. Furthermore, more than 30 candidate-gene studies have been performed, mainly attempting to replicate variants discovered in GWAS or candidate genes likely involved in the corticosteroid drug pathway. Single nucleotide polymorphisms located in GLCCI1, NR3C1 and the 17q21 locus were positively replicated in independent populations. Although none of the genetic markers has currently reached clinical practise, these studies might provide novel insights in the complex pathways underlying corticosteroids response in asthmatic patients.