Reslizumab in the treatment of patients with severe eosinophilic asthma phenotype

Abstract

It is known that patients with severe asthma often fail to achieve disease control. Excessive airways eosinophilic inflammation is one of the key causes of severe uncontrolled asthma in this case. The occurrence of eosinophilic phenotype of inflammation is quite high in severe uncontrolled asthma. Thus, about 55% of patients have eosinophil level in induced sputum ≥ 3%. Eosinophilic phenotype of asthma is associated with greater severity of symptoms, presence of atopy, late onset of the disease, and lack of response to inhaled glucocorticosteroids. Numerous studies confirmed the relationship between elevated eosinophils in the airways and more frequent and severe asthma exacerbations, as well as reduced lung function, increased administration of steroids and other medications, and more frequent use of healthcare services. Severe eosinophilic asthma is characterized mainly by late onset of the disease, persistent eosinophilia in the airways and peripheral blood. It is associated with frequent exacerbations, chronic or intermittent need to the use of systemic corticosteroids to achieve better control of the disease, and unfavorable prognosis of the natural course. Predominantly eosinophilic type of airway inflammation is a characteristic manifestation of T2 endotype of asthma, that is implemented due to the domination of Th2-lymphocyte response (allergic asthma) and/or due to high activity of type 2 innate lymphoid cells (ILC2) involved in the development of both non-allergic and allergic asthma. Th2 and ILC2 cells increase IL-5 level, which plays an important role in the formation of uncontrolled eosinophilic inflammation in the airways in patients suffering from T2 endotype of severe asthma, by stimulating eosinophil precursor maturation in the bone marrow, mobilization of eosinophils and precursors from the bone marrow, accumulation of eosinophils in the blood, eosinophilic infiltration of lung tissue, and eosinophil migration in the area of inflammation. The novel medication reslizumab (Cinqair) is the first anti-IL-5 immunological biologic drug registered in Russia for the treatment of severe asthma with eosinophilic airway inflammation. As a humanized monoclonal antibody (IgG4k) with high affinity for IL-5, reslizumab specifically binds to IL-5 and inhibits its interaction with IL-5 receptor on the cell surface, thus disrupting the underlying pathophysiology of bronchial inflammation in asthma, including maturation and survival of eosinophils, inflammation and remodeling of the airways. Clinical effects of reslizumab are manifested as decreased asthma exacerbation rate, improved lung function, and disease control.