Abstract

Human eosinophils represent approximately 1% of peripheral blood leukocytes. However, these cells have the propensity to leave the blood stream and migrate into inflamed tissues. Eosinophilic inflammation is present in a significant proportion of patients with severe asthma. Asthma is a chronic inflammatory disorder that affects more than 315 million people worldwide, with 10% having severe uncontrolled disease. Although the majority of patients can be efficiently treated, severe asthmatics continue to be uncontrolled and are at risk of exacerbations and even death. Interleukin-5 (IL-5) plays a fundamental role in eosinophil differentiation, maturation, activation and inhibition of apoptosis. Therefore, targeting IL-5 is an appealing approach to the treatment of patients with severe eosinophilic asthma. Reslizumab, a humanized anti-IL-5 monoclonal antibody, binds with high affinity to amino acids 89–92 of IL-5 that are critical for binding to IL-5 receptor α. Two phase III studies have demonstrated that reslizumab administration in adult patients with severe asthma and eosinophilia (≥400 cells/μL) improved lung function, asthma control, and symptoms. Thus, the use of blood eosinophils as a baseline biomarker could help to select patients with severe uncontrolled asthma who are likely to achieve benefits in asthma control with reslizumab. In conclusion, targeted therapy with reslizumab represents one step closer to precision medicine in patients with severe eosinophilic asthma.

Highlights

  • Bronchial asthma is a chronic heterogeneous inflammatory disorder characterized by recurrent symptoms of reversible airflow obstruction, bronchial hyperresponsiveness, and airway inflammation [1, 2]

  • Two humanized monoclonal antibodies directed against IL-5 [mepolizumab and reslizumab] have provided an opportunity to investigate the role of this pathway in defining therapy of severe eosinophilic asthma [44, 51]

  • Benralizumab (MedImmune/AstraZeneca), a humanized monoclonal antibody directed against the α-chain of the IL-5 receptor (IL-5R), present on eosinophils and basophils [52], demonstrated efficacy and safety in adult patients with severe eosinophilic asthma [53, 54]

Read more

Summary

Introduction

Bronchial asthma is a chronic heterogeneous inflammatory disorder characterized by recurrent symptoms of reversible airflow obstruction, bronchial hyperresponsiveness, and airway inflammation [1, 2]. 5–10% of asthmatic patients have severe asthma that is poorly controlled by drugs including high-dosage of ICS and/or systemic glucocorticoids. Two humanized monoclonal antibodies directed against IL-5 [mepolizumab (proposed trade name Nucala; GSK) and reslizumab (proposed trade name Cinqair; Teva)] have provided an opportunity to investigate the role of this pathway in defining therapy of severe eosinophilic asthma [44, 51].

Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call