Biological therapies targeting the type 2 inflammatory pathway in severe asthma (Review)

Abstract

Asthma is a variable chronic respiratory disease characterized by airway inflammation and hyperresponsiveness, bronchoconstriction, and mucus hypersecretion. While most patients with asthma achieve good control of the disease, 5-10% experience severe symptoms and recurrent exacerbation despite the maximal offered therapy with inhaled corticosteroids and long acting bronchodilators. In previous years, novel biological therapies have become available, and various asthma phenotypes that are characterized by specific biomarkers have been identified. Currently approved biological agents target inflammatory molecules of the type 2 inflammatory pathway, and are effective at decreasing the frequency of asthma attacks, controlling symptoms and decreasing use of systemic steroids. The present study reviewed the effectiveness and safety profile of the currently approved biological drugs and provided an overview of the assessment of patients with severe asthma who are potentially suitable for biological therapy, in order to help clinicians to select the most appropriate biological agent. Contents1. Introduction 2. Pathophysiology of severe asthma 3. Targeting T2 severe asthma phenotypes-currently approved treatments and biological drugs under investigation 4. Discussion 5. Conclusion

Specific Therapy for T2 Asthma

“…Mepolizumab (MEP) is a humanized monoclonal antibody, belonging to the class of IgG1κ, able to block the interaction between the α-subunit and IL-5R on the eosinophil cell surface. The inhibiting action of the drug induces an inactivation of eosinophil maturation, activation and growth [7,33]. MEP is given at the dose of 100 mg subcutaneously every 4 weeks, in patients > 12 years old, with severe asthma and a number of eosinophils greater than 300 cells/µL in the year previous to the administration and at least 150 cells/µL at the moment of first dose.…”

“…The knowledge of the mechanisms underlying the disease and of the spectrum of cytokines involved in the development of the pathology, made possible to use the latter as a therapeutic target to control patients with difficult-to-control asthma. Essentially, the available therapeutic options, for severe asthmatic people, are monoclonal antibodies (MABs) targeting Immunoglobulin E (IgE), IL-5 or its receptor alpha and IL-4/13 receptor [7]. The principal objective of biological therapies in severe asthma is to ensure disease control in terms of annual exacerbations, use of systemic corticosteroids (CS) either taken daily or in cycles, in case of acute phases of the disease.…”

Advances and Highlights of miRNAs in Asthma: Biomarkers for Diagnosis and Treatment

“…Nowadays, it is very important to phenotype individuals with type 2 or eosinophilic asthma, as in recent years specific biological treatments have been developed for them. These biologics target eosinophils directly or indirectly by modulating the levels of different mediators implicated in this type of asthma [ 5 ].…”

Real-World clinical outcomes of asthma patients switched from reslizumab to mepolizumab or benralizumab

“…This group, known as severe refractory asthmatics, have derived clinical benefit from drugs aimed at the interleukins and receptors activated in T2 inflammatory pathways. Current available treatments for severe refractory asthmatics include monoclonal antibodies (mAb) which target IL-5 (reslizumab and mepolizumab), the IL-5 receptor (benralizumab), the IL-4/13 receptor (dupilumab) or immunoglobulin E (IgE) (omalizumab) ( 5 ).…”

“…Mepolizumab is a mAb which blocks the interaction between the α -subunit and the IL-5 receptor on the surface of the eosinophil thereby preventing eosinophil maturation and activation ( 5 , 10 ). Clinical trials demonstrated mepolizumab's ability to reduce the frequency of exacerbation and reduce OCS use in those with SEA ( 11 – 13 ).…”