Benralizumab in the treatment of severe asthma: design, development and potential place in therapy

被引:52
作者
Pelaia, Corrado [1 ]
Vatrella, Alessandro [2 ]
Bruni, Andrea [1 ]
Terracciano, Rosa [3 ]
Pelaia, Girolamo [1 ]
机构
[1] Magna Graecia Univ Catanzaro, Sect Resp Dis, Dept Med & Surg Sci, Catanzaro, Italy
[2] Univ Salerno, Sect Resp Dis, Dept Med Surg & Dent, Salerno, Italy
[3] Magna Graecia Univ Catanzaro, Dept Hlth Sci, Catanzaro, Italy
关键词
IL-5; receptor; severe eosinophilic asthma; benralizumab; CELL-MEDIATED CYTOTOXICITY; SEVERE EOSINOPHILIC ASTHMA; ALPHA MONOCLONAL-ANTIBODY; ACTIVATED PROTEIN-KINASE; ANTI-INTERLEUKIN-5; RECEPTOR; CRYSTAL-STRUCTURE; DOUBLE-BLIND; INTERLEUKIN-5; IL-5; INFLAMMATION;
D O I
10.2147/DDDT.S155307
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Asthma is a widespread and heterogeneous inflammatory disease of the airways, which is characterized by several different phenotypes and endotypes. In particular, eosinophilic airway inflammation is a common pathologic trait of both allergic and nonallergic asthma. The key cytokine responsible for maturation, activation, recruitment, and survival of eosinophils is interleukin (IL)-5, which is mainly produced by T helper 2 (Th2) lymphocytes and group 2 innate lymphoid cells. Therefore, for uncontrolled patients with severe eosinophilic asthma, who are not fully responsive to corticosteroids, IL-5 represents a very important molecular target for add-on biological therapies. Among these new treatments, anti-IL-5 monoclonal antibodies such as mepolizumab and reslizumab have been developed and clinically evaluated. Furthermore, benralizumab is currently the only available biologic drug that specifically binds to the IL-5 receptor, thus preventing the interaction with its ligand and the consequent pro-inflammatory effects. The effectiveness of benralizumab in improving severe eosinophilic asthma has been well-documented by many randomized controlled trials.
引用
收藏
页码:619 / 628
页数:10
相关论文
共 70 条
[1]   The differential role of extracellular signal-regulated kinases and p38 mitogen-activated protein kinase in eosinophil functions [J].
Adachi, T ;
Choudhury, BK ;
Stafford, S ;
Sur, S ;
Alam, R .
JOURNAL OF IMMUNOLOGY, 2000, 165 (04) :2198-2204
[2]   The mechanism of IL-5 signal transduction [J].
Adachi, T ;
Alam, R .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1998, 275 (03) :C623-C633
[3]   Eosinophilic asthma: Insights into the effects of reducing IL-5 receptor-positive cell levels [J].
Assa'ad, Amal H. ;
Rothenberg, Marc E. .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2013, 132 (05) :1097-1098
[4]   ERK1 and ERK2 activation by chemotactic factors in human eosinophils is interleukin 5-dependent and contributes to leukotriene C4 biosynthesis [J].
Bates, ME ;
Green, VL ;
Bertics, PJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (15) :10968-10975
[5]   New Anti-Eosinophil Drugs for Asthma and COPD Targeting the Trait! [J].
Bel, Elisabeth H. ;
ten Brinke, Anneke .
CHEST, 2017, 152 (06) :1276-1282
[6]   Oral Glucocorticoid-Sparing Effect of Mepolizumab in Eosinophilic Asthma [J].
Bel, Elisabeth H. ;
Wenzel, Sally E. ;
Thompson, Philip J. ;
Prazma, Charlene M. ;
Keene, Oliver N. ;
Yancey, Steven W. ;
Ortega, Hector G. ;
Pavord, Ian D. .
NEW ENGLAND JOURNAL OF MEDICINE, 2014, 371 (13) :1189-1197
[7]   Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial [J].
Bleecker, Eugene R. ;
FitzGerald, J. Mark ;
Chanez, Pascal ;
Papi, Alberto ;
Weinstein, Steven F. ;
Barker, Peter ;
Sproule, Stephanie ;
Gilmartin, Geoffrey ;
Aurivillius, Magnus ;
Werkstrom, Viktoria ;
Goldman, Mitchell .
LANCET, 2016, 388 (10056) :2115-2127
[8]   EOSINOPHILIC INFLAMMATION IN ASTHMA [J].
BOUSQUET, J ;
CHANEZ, P ;
LACOSTE, JY ;
BARNEON, G ;
GHAVANIAN, N ;
ENANDER, I ;
VENGE, P ;
AHLSTEDT, S ;
SIMONYLAFONTAINE, J ;
GODARD, P ;
MICHEL, FB .
NEW ENGLAND JOURNAL OF MEDICINE, 1990, 323 (15) :1033-1039
[9]   Eosinophilic airway inflammation in nonallergic asthma [J].
Brusselle, Guy G. ;
Maes, Tania ;
Bracke, Ken R. .
NATURE MEDICINE, 2013, 19 (08) :977-979
[10]   Safety profile, pharmacokinetics, and biologic activity of MEDI-563, an anti-IL-5 receptor α antibody, in a phase I study of subjects with mild asthma [J].
Busse, William W. ;
Katial, Rohit ;
Gossage, David ;
Sari, Suha ;
Wang, Bing ;
Kolbeck, Roland ;
Coyle, Anthony J. ;
Koike, Masamichi ;
Spitalny, George L. ;
Kiener, Peter A. ;
Geba, Gregory P. ;
Molfino, Nestor A. .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2010, 125 (06) :1237-1244