Targeting eosinophils: severe asthma and beyond

Abstract

Recent research in the field of bronchial asthma has mainly focused on eosinophilic disease phenotype. Several trials proved the efficacy and safety profile of eosinophils and interleukin (IL)-5 targeting molecules, currently approved for severe asthma and available on the market. They include mepolizumab and reslizumab, IL-5 blocking molecules, and benralizumab, targeting the IL-5 receptor and eliciting a NK cell-mediated antibody-dependent cellular cytotoxicity against eosinophils. Eosinophilic inflammation represents the common pathophysiological background of several conditions, providing the rationale for the use of the same biologics beyond asthma. Although with different evidence grade, from clinical trials to case reports, anti-IL-5 biologics have been investigated in eosinophilic granulomatosis with polyangitis, allergic bronchopulmonary aspergillosis, chronic eosinophilic pneumonia, nasal polyposis, hypereosinophilic syndrome, and eosinophilic esophagitis. However, non-negligible differences between asthma and other eosinophilic diseases, particularly in eosinophils homing (blood and/or tissues), target organs and thus clinical features, probably account for the different response to the same drug in different clinical conditions and highlights the need for tailoring the therapeutic approach by modulating the drug dose and/or by combination therapy with multiple drugs. The optimal safety and tolerability profile of anti-IL-5 drugs warrants further and larger experimental and real-life investigations, which are needed especially in the field of non-asthma eosinophilic diseases. This review aims at summarizing the rationale for the use of biologics in eosinophilic diseases and their mechanisms of action. The current efficacy and safety evidence about eosinophils and IL-5 targeting molecules in asthma and in eosinophilic conditions beyond bronchi is also discussed.

Clinical Experience in the Treatment of Severe Eosinophilic Asthma With Mepolizumab

“…The total number of eosinophils in blood at basal situation was 856 cels/mm 3 (SD 754) and after treatment it decreased to 101 (SD 98). In the case of the patients considered as responsive, the initial figure was 812 cels/mm 3 (SD 194) at onset decreasing to 42 cels/mm 3 (SD 34) after starting treatment.…”

“…Conventional treatment of asthma basically includes the use of corticosteroids and beta-2 agonists, although sometimes the severity of the process and the recurrence of exacerbations requires the addition of other drugs and the use of oral corticosteroids (OCS) (2). In some patients, with high levels of eosinophils in blood and sputum, the use of a drug ( Mepolizumab) is indicated whose function is to block interleukin 5 (IL-5), and, in this way, avoid the mobility and the passage of the eosinophils towards the airways (3,4). The experience with Mepolizumab comes from diverse published clinical trials (5)(6)(7)(8)(9) as well as the clinical use in different countries (10,11).…”

Initiation and Pathogenesis of Severe Asthma with Fungal Sensitization

“…Most SAFS patients have heightened eosinophilic inflammation [137]. While SAFS is generally nonresponsive to corticosteroids, the advent of anti-eosinophilic biologics has led to better management of asthma severity in SAFS patients [169]. The knowledge that eosinophils play a host-protective role during virus infections [142,170], including IAV infections [91,141,171] and possibly SARS-CoV-2 infection [172], raises the question of whether fungal allergen-induced eosinophilia has some benefit, at least seasonally, and if so, what the possible long-term complications may be of eliminating eosinophils in SAFS patients [173].…”

A case of allergic bronchopulmonary aspergillosis with marked peripheral blood eosinophilia successfully treated with benralizumab

“…Benralizumab is an IgG1κ mAb that targets the epitope of the α subunit of the IL-5 receptor on the eosinophil surface and inhibits IL-5-mediated cell proliferation [ 15 ]. In addition, benralizumab can activate NK cells and macrophages to induce antibody-dependent cytotoxicity (ADCC) against both eosinophils and basophils [ 16 , 17 ]. As a result, within 24 hours of the first dose of benralizumab, the blood eosinophils were completely depleted, and sputum and tissues were almost completely depleted [ 18 ].…”