Reductions in eosinophil biomarkers by benralizumab in patients with asthma

Pham, Tuyet‐Hang; Damera, Gautam; Newbold, Paul; Ranade, Koustubh

doi:10.1016/j.rmed.2016.01.003

Cited by 164 publications

(117 citation statements)

References 39 publications

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“…Benralizumab (AstraZeneca, Cambridge, UK) is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody that induces direct, rapid, and nearly complete depletion of eosinophils via enhanced antibody-dependent cell-mediated cytotoxicity [11,12]. Benralizumab 30 mg every 8 weeks (Q8W; first three doses every 4 weeks [Q4W]) is indicated for the add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype [13].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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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.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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“…Moreover, eosinophil‐derived neurotoxin (EDN) has been shown to be a useful biomarker of eosinophilic inflammation in a wide variety of clinical samples . The 2 eosinophil activation markers mentioned above are more closely linked to IL‐5 production, but might reflect different aspects, as EDN relates mainly to lung function, while S‐ECP relates to symptoms and asthma attacks …”

Section: Introductionmentioning

confidence: 99%

IgE sensitization to food allergens and airborne allergens in relation to biomarkers of type 2 inflammation in asthma

Patelis

Alving

Middelveld

et al. 2018

Clin Experimental Allergy

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“…An argument against a dominant role of immune complexes in modulating IL‐5 levels in vivo came from data of a study on treating patients with benralizumab. Also in these patients, treatment with this antibody independently of the dose (25‐200 mg) resulted in a clear increase in serum level of IL‐5 while treating a similar cohort of patients with placebo did not . The increase in serum/plasma IL‐5 regardless of its cause during treatment with anti‐IL‐5(Rα) might have clinical consequences.…”

Section: Effect Of Il‐5(rα)‐targeted Therapy On Il‐5 Levels In Blood mentioning

confidence: 90%

“…Treatment with anti‐IL‐5Rα antibodies (benralizumab) also caused a decreased concentration of ECP and eosinophil‐derived neurotoxin (EDN) in serum, meaning that despite ADCC, no harmful proteins are released in blood …”

Section: Effect Of Anti‐il‐5(receptor) On Cellular Priming and Activamentioning

confidence: 99%

Immunological and hematological effects of IL‐5(Rα)‐targeted therapy: An overview

Hassani

Koenderman

2018

Allergy

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IL‐5 is an important cytokine for priming and survival of mature eosinophils and for proliferation and maturation of their progenitors. Hence, IL‐5(Rα) targeting will be increasingly used in diseases where eosinophils are the key immune effector cells such as eosinophilic asthma (EA), hypereosinophilic syndrome (HES), eosinophilic esophagitis (EE), and eosinophilic granulomatosis with polyangiitis (EGPA). Therefore, several neutralizing monoclonal antibodies directed against IL‐5 (mepolizumab and reslizumab) and its receptor IL‐5Rα (benralizumab) have found or will find their way to the clinic. While the clinical effect of these drugs has been extensively investigated and reviewed, the understanding of the underlying immunological and hematological mechanisms remains less clear. This review will discuss the translational outcomes of treatment with these monoclonal antibodies in humans to shed light on the mechanisms underlying the main immunological and hematological findings from these clinical trials in humans.

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Reductions in eosinophil biomarkers by benralizumab in patients with asthma

Cited by 164 publications

References 39 publications

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

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

IgE sensitization to food allergens and airborne allergens in relation to biomarkers of type 2 inflammation in asthma

Immunological and hematological effects of IL‐5(Rα)‐targeted therapy: An overview

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