Benralizumab: A New Approach for the Treatment of Severe Eosinophilic Asthma

Abstract

Eosinophilic asthma is the most common phenotype of severe asthma. It is characterized by abnormal production and release of type 2 cytokines from T helper type 2 (T H 2) lymphocytes and type 2 innate lymphoid cells, such as IL-5. This leads to a persistent increase and activation of eosinophils in blood and the airways despite treatment with high-dose inhaled corticosteroids. Eosinophil differentiation, survival, and activation are preferentially regulated by IL-5, a cytokine that binds to the IL-5 receptor (IL-5R), which is located on the surface of eosinophils or basophils and plays a critical role in the pathogenesis and severity of asthma. Benralizumab is a monoclonal antibody that binds to IL-5R via its Fab domain, blocking the binding of IL-5 to its receptor and resulting in inhibition of eosinophil differentiation and maturation in bone marrow. In addition, this antibody is able to bind through its afucosylated Fc domain to the RIIIa region of the Fc receptor on NK cells, macrophages, and neutrophils, thus strongly inducing antibody-dependent, cell-mediated cytotoxicity in both circulating and tissue-resident eosinophils. This double function of benralizumab induces almost complete fast and maintained depletion of eosinophils that is much greater than that induced by other monoclonal antibodies targeting the IL-5 pathway, such as mepolizumab and reslizumab. This review focuses on benralizumab as an alternative to other agents targeting the IL-5 pathway in the treatment of eosinophilic asthma.

Interleukin-5 in the Pathophysiology of Severe Asthma

“…Several phase 3 RCT have recently shown that, as add-on treatment of severe eosinophilic asthma, benralizumab is characterized by an excellent pattern of efficacy, safety, and tolerability (Pelaia et al, 2018b,c;Gonzalez et al, 2019). In particular, CALIMA and SIROCCO trials showed that benralizumab significantly decreased the annual rate of severe eosinophilic exacerbations of asthma, and also improved asthma symptom control and enhanced FEV 1 (Bleecker et al, 2016;FitzGerald et al, 2016).…”

Personalized Approach of Severe Eosinophilic Asthma Patients Treated with Mepolizumab and Benralizumab

“…The best known pathogenic mechanism involved in severe asthma development is mediated by eosinophils and IL-5 [6]. New anti-eosinophilic monoclonal antibodies, mepolizumab and benralizumab, have recently been approved to reduce exacerbations and to improve lung function in patients with severe and uncontrolled asthma with eosinophilic inflammation [7-9]. The 2 drugs have different mechanisms of action: mepolizumab blocks the activity of circulating cytokine IL-5 and benralizumab interferes with the IL-5 receptor alpha (IL-5Rα) of eosinophils [10, 11].…”

Rapid and remarkable effectiveness of benralizumab for treating severe bronchial asthma with intractable eosinophilic rhinosinusitis and eosinophilic otitis media: A case report

“…Since her airway and ear inflammation might be related to type 2 inflammation and her IgE level was low, anti-IL-5 biologic therapy was selected for the add-on therapy as recommended by GINA [ 1 ]. Benralizumab, an monoclonal antibody to IL-5 receptor α (IL-5Rα) on eosinophils and also binds the RIIIa region of the FCγ receptor (FcγRIIIa) on natural killer cells, macrophages and neutrophils with a high affinity [ 23 ], was used in our case, and nearly complete depletion of eosinophils in the peripheral blood was achieved through enhanced antibody-dependent cell-mediated cytotoxicity [ 24 ]. Following depletion of eosinophils in the peripheral blood, asthma control, asthma-related QOL, and pulmonary function dramatically improved in a month ( Table 1 ).…”

“…This antibody also binds to the FcγRIIIa receptor on natural killer cells, macrophages, and neutrophils, inducing antibody-dependent cellular cytotoxicity to eosinophils. This double-function, which is different from other IL-5 antagonist such as mepolizumab and reslizumab [ 23 ], might have induced the near-complete deletion of eosinophils from the patient's airways and provided rapid symptomatic relief. Although therapy with anti-IL-5 antibodies are greatly effective for treating type 2 inflammation by suppressing eosinophilic infiltration [ 23 , 24 ], the bottle neck of using these drugs is the high cost of treatment.…”

“…This double-function, which is different from other IL-5 antagonist such as mepolizumab and reslizumab [ 23 ], might have induced the near-complete deletion of eosinophils from the patient's airways and provided rapid symptomatic relief. Although therapy with anti-IL-5 antibodies are greatly effective for treating type 2 inflammation by suppressing eosinophilic infiltration [ 23 , 24 ], the bottle neck of using these drugs is the high cost of treatment. The official cost of benralizumab is 358,045 Japanese yen (~3400 US dollar) for one ampule (30 mg), which is used once per month for the first 3 months, and bimonthly thereafter.…”