Ability of Serum IgE Concentration to Predict Exacerbation Risk and Benralizumab Efficacy for Patients with Severe Eosinophilic Asthma

Abstract

Introduction: For patients with eosinophilic asthma with allergic characteristics, understanding the key drivers of exacerbations is important to identify optimal treatment strategies. Benralizumab is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody that significantly reduces exacerbation frequency for patients with severe, uncontrolled eosinophilic asthma. We evaluated the predictive value of baseline blood eosinophil counts vs. serum immunoglobulin E (IgE) concentrations on exacerbation risk and the association of these variables with benralizumab treatment effect. Methods: Analyses were performed with data pooled from the phase III SIROCCO and CALIMA benralizumab trials. Crude annual asthma exacerbation rates (AERs) were determined for placebo as a function of baseline blood eosinophil counts and serum IgE concentrations with prespecified blood eosinophil count categories (\ 150, C 150 to \ 300, C 300 to \ 450, C 450 cells/lL) and IgE concentration quartiles (\ 62.0, C 62.0 to \ 176.2, C 176.2 to \ 453.4, and C 453.4 kU/L). We compared AERs for patients receiving benralizumab 30 mg every 8 weeks (first three doses every 4 weeks) vs. placebo for overlapping baseline blood eosinophil count categories and serum IgE concentration quartiles via a regression approach and by continuously using locally weighted regression smoothing analysis.

Therapeutic Effects of Benralizumab Assessed in Patients with Severe Eosinophilic Asthma: Real-Life Evaluation Correlated with Allergic and Non-Allergic Phenotype Expression

“…Hence, also these findings corroborate the results of recent pooled analyses of SIROCCO and CALIMA trials, which showed that the therapeutic effects of benralizumab were independent of IgE levels and atopic trait in subjects with severe eosinophilic asthma. 29 , 60 …”

The Predictive Role of Biomarkers and Genetics in Childhood Asthma Exacerbations

“…However, B-Eos have been shown to be significantly predictive of sputum eosinophilia [ 21 ]. In adults, numerous works observed the association between elevated B-Eos and asthma attacks, with increasing rate of hospitalization [ 24 , 42 , 43 ]. In childhood, the role of blood eosinophils in the prediction of asthma exacerbations has long been unclear.…”

“…In childhood, the role of blood eosinophils in the prediction of asthma exacerbations has long been unclear. Some studies stated the validity of this association in children and adolescents [ 18 , 19 , 22 , 24 ]; however, the cut-point of blood eosinophils for clinical detection of type 2 inflammation was not precisely determined. A retrospective study of children 5 to 11 years in a large medical care organization compared different B-Eos thresholds and identified an optimal cut-off of 300 cells/mL, which was associated with a 52% increase in asthma exacerbation rate [ 21 ].…”

“…A retrospective study of children 5 to 11 years in a large medical care organization compared different B-Eos thresholds and identified an optimal cut-off of 300 cells/mL, which was associated with a 52% increase in asthma exacerbation rate [ 21 ]. The same limit value was utilized by other authors [ 19 , 20 , 24 ]. Interestingly, Pavord et al in DREAM trial studied 621 patients aged 12–74 years and considered B-Eos count > 300 cells/mL as a biomarker to identify subjects with recurrent asthma exacerbations eligible to Mepolizumab therapy.…”

Severe uncontrolled allergic eosinophilic asthma – looking for the best therapeutic option

“…Jak pokazują metaanalizy, terapie antyeozynofilowe skierowane przeciwko IL-5 (mepolizumab, reslizumab) lub łańcuchowi α receptora dla IL-5 (benralizumab) redukują liczbę ciężkich zaostrzeń o połowę [44]. Efektywność terapii antyeozynofilowych potwierdzono zarówno w astmie atopowej, jak i nieatopowej, bez istotnej różnicy pomiędzy grupami [45,46].…”