2019
DOI: 10.2147/btt.s157183
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<p>New horizons for the treatment of severe, eosinophilic asthma: benralizumab, a novel precision biologic</p>

Abstract: In the last decades, the increasing evidence concerning inflammation mechanisms underlying severe eosinophilic asthma has highlighted new potential therapeutic targets and has paved the way to new selective biologic drugs. Understanding the mechanism of action and the clinical outcomes of a particular drug along with the clinical and biological characteristics of the patient population for which that drug was intended may ensure appropriate selection of patients that will respond to that drug. Under this persp… Show more

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Cited by 12 publications
(11 citation statements)
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“…The advent of monoclonal antibodies (mAbs) targeting the interleukin-5 (IL-5) pathway has provided a new phenotype-specific approach. Unlike the anti-IL-5 mAbs mepolizumab [ 15 ] and reslizumab [ 16 ], benralizumab [ 17 ] targets IL-5 receptor alpha (IL-5Rα), which is highly expressed by human eosinophils and eosinophil progenitors [ 6 ], and has the unique ability to induce rapid and complete depletion of blood and tissue eosinophils, and of other IL-5Rα + cells as well, via afucosylation-dependent Ab-dependent cell-mediated cytotoxicity (ADCC) [ 18 , 19 ]. In the pivotal phase 3 trials, benralizumab as add-on maintenance treatment in patients with uncontrolled SEA decreased the annual exacerbation rate (AER) by up to 70%, improved lung function and asthma symptoms, and allowed a 75% reduction in the median dose of OCS (discontinuation rate: 52%), with a good safety and tolerability profile [ 20 22 ].…”
Section: Introductionmentioning
confidence: 99%
“…The advent of monoclonal antibodies (mAbs) targeting the interleukin-5 (IL-5) pathway has provided a new phenotype-specific approach. Unlike the anti-IL-5 mAbs mepolizumab [ 15 ] and reslizumab [ 16 ], benralizumab [ 17 ] targets IL-5 receptor alpha (IL-5Rα), which is highly expressed by human eosinophils and eosinophil progenitors [ 6 ], and has the unique ability to induce rapid and complete depletion of blood and tissue eosinophils, and of other IL-5Rα + cells as well, via afucosylation-dependent Ab-dependent cell-mediated cytotoxicity (ADCC) [ 18 , 19 ]. In the pivotal phase 3 trials, benralizumab as add-on maintenance treatment in patients with uncontrolled SEA decreased the annual exacerbation rate (AER) by up to 70%, improved lung function and asthma symptoms, and allowed a 75% reduction in the median dose of OCS (discontinuation rate: 52%), with a good safety and tolerability profile [ 20 22 ].…”
Section: Introductionmentioning
confidence: 99%
“…In addition, eosinophils differentiate and mature in the bone marrow, for suppressing the lung infiltration of eosinophils. Mepolizumab and benralizumab are antibody preparations that target IL-5 and IL-5R and have been used in the treatment of asthma [30,31]. Therefore, we focused on the Th2 cytokine, IL-5, as a key player in fasting induced suppression of eosinophil infiltration.…”
Section: Discussionmentioning
confidence: 99%
“…As a result, eosinophilia is reduced in blood, tissue and bone marrow due to the inhibition of eosinophil differentiation and maturation. In addition, benralizumab also depletes eosinophils in tissues and systemic circulation via antibody-dependent, cell-mediated cytotoxicity as it can bind to the RIIIa region of the Fc receptor on NK cells, neutrophils and macrophages through its afucosylated Fc domain (97,98). The dual-function of benralizumab allows for a more rapid and sustained reduction of eosinophilia than other IL-5-targeted monoclonal antibodies (97).…”
Section: Benralizumabmentioning
confidence: 99%
“…Thus, benralizumab is shown to J o u r n a l P r e -p r o o f selectively modulate blood proteins and eosinophil-or basophil-associated genes, with alterations occurring prominently in eosinophil-high patients rather than eosinophil-low patients (99). Randomized clinical trials have also provided evidence on the optimal safety profile of benralizumab, as well as its efficacy in reducing asthma exacerbations, steroidsparing and improvement of lung function (98). When compared to reslizumab, benralizumab was associated with a significantly improved lung function in asthma patients with severe eosinophilia (≥400 cells/μL) (95).…”
Section: Benralizumabmentioning
confidence: 99%