Lebrikizumab in the personalized management of asthma

Neil C Thomson,1 Manish Patel,2 Andrew D Smith21Institute of Infection, Immunity, and Inflammation, University of Glasgow and Respiratory Medicine, Gartnavel General Hospital, Glasgow, UK; 2Department of Respiratory Medicine, Wishaw Hospital, Wishaw, Lanarkshire, UKAbstract: There is a need for impr...

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Autores principales:	Thomson NC, Patel M, Smith AD
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/cee825f901ba45e4abab67fd7204c126
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spelling	oai:doaj.org-article:cee825f901ba45e4abab67fd7204c1262021-12-02T11:32:17ZLebrikizumab in the personalized management of asthma1177-54751177-5491https://doaj.org/article/cee825f901ba45e4abab67fd7204c1262012-09-01T00:00:00Zhttp://www.dovepress.com/lebrikizumab-in-the-personalized-management-of-asthma-a11006https://doaj.org/toc/1177-5475https://doaj.org/toc/1177-5491Neil C Thomson,1 Manish Patel,2 Andrew D Smith21Institute of Infection, Immunity, and Inflammation, University of Glasgow and Respiratory Medicine, Gartnavel General Hospital, Glasgow, UK; 2Department of Respiratory Medicine, Wishaw Hospital, Wishaw, Lanarkshire, UKAbstract: There is a need for improved therapies for severe asthma. Lebrikizumab, a humanized monoclonal antibody that binds to interleukin (IL)-13, is under development for the treatment of poorly controlled asthma. This article reviews the potential role of IL-13 in the pathogenesis of asthma, the efficacy and safety of lebrikizumab in humans, and progress in patient selection for lebrikizumab therapy. IL-13 is a T-helper (Th2) cell-derived cytokine implicated in inflammatory responses in asthma, including serum immunoglobulin-E synthesis, mucus hypersecretion, and subepithelial fibrosis. Blocking the pro-inflammatory effects of IL-13 with lebrikizumab has the potential to improve asthma control. Published data on the efficacy and safety of lebrikizumab in the treatment of asthma are relatively limited. The late asthmatic response after inhaled allergen challenge is reduced by almost 50%, following treatment with lebrikizumab. In a Phase II study performed in 219 adults with poorly controlled asthma despite inhaled corticosteroids (MILLY trial), lebrikizumab produced an improvement in prebronchodilator forced expiratory volume in 1 second of 5.5% compared with placebo at 12 weeks, but had no effects on other efficacy end points. Adverse effects were similar to placebo, except that musculoskeletal side effects occurred slightly more often with lebrikizumab. Stratifying patients into a high Th2 phenotype using serum periostin, which is upregulated in lung epithelial cells by IL-13, may identify individuals responsive to blockade of IL-13. In the MILLY trial, lebrikizumab treatment was associated with greater improvement in lung function in patients with elevated serum periostin levels compared with those with low periostin levels. Two large Phase III randomized controlled trials in patients with uncontrolled asthma are underway to establish the safety and efficacy of lebrikizumab when administered over a 52-week period. These studies will also help to determine whether identifying patients with a Th2 high inflammatory phenotype using serum periostin allows a personalized approach to the treatment of asthma.Keywords: asthma, periostin, interleukin-13, phenotypes, exhaled nitric oxide, lebrikizumabThomson NCPatel MSmith ADDove Medical PressarticleMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol 2012, Iss default, Pp 329-335 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Thomson NC Patel M Smith AD Lebrikizumab in the personalized management of asthma
description	Neil C Thomson,1 Manish Patel,2 Andrew D Smith21Institute of Infection, Immunity, and Inflammation, University of Glasgow and Respiratory Medicine, Gartnavel General Hospital, Glasgow, UK; 2Department of Respiratory Medicine, Wishaw Hospital, Wishaw, Lanarkshire, UKAbstract: There is a need for improved therapies for severe asthma. Lebrikizumab, a humanized monoclonal antibody that binds to interleukin (IL)-13, is under development for the treatment of poorly controlled asthma. This article reviews the potential role of IL-13 in the pathogenesis of asthma, the efficacy and safety of lebrikizumab in humans, and progress in patient selection for lebrikizumab therapy. IL-13 is a T-helper (Th2) cell-derived cytokine implicated in inflammatory responses in asthma, including serum immunoglobulin-E synthesis, mucus hypersecretion, and subepithelial fibrosis. Blocking the pro-inflammatory effects of IL-13 with lebrikizumab has the potential to improve asthma control. Published data on the efficacy and safety of lebrikizumab in the treatment of asthma are relatively limited. The late asthmatic response after inhaled allergen challenge is reduced by almost 50%, following treatment with lebrikizumab. In a Phase II study performed in 219 adults with poorly controlled asthma despite inhaled corticosteroids (MILLY trial), lebrikizumab produced an improvement in prebronchodilator forced expiratory volume in 1 second of 5.5% compared with placebo at 12 weeks, but had no effects on other efficacy end points. Adverse effects were similar to placebo, except that musculoskeletal side effects occurred slightly more often with lebrikizumab. Stratifying patients into a high Th2 phenotype using serum periostin, which is upregulated in lung epithelial cells by IL-13, may identify individuals responsive to blockade of IL-13. In the MILLY trial, lebrikizumab treatment was associated with greater improvement in lung function in patients with elevated serum periostin levels compared with those with low periostin levels. Two large Phase III randomized controlled trials in patients with uncontrolled asthma are underway to establish the safety and efficacy of lebrikizumab when administered over a 52-week period. These studies will also help to determine whether identifying patients with a Th2 high inflammatory phenotype using serum periostin allows a personalized approach to the treatment of asthma.Keywords: asthma, periostin, interleukin-13, phenotypes, exhaled nitric oxide, lebrikizumab
format	article
author	Thomson NC Patel M Smith AD
author_facet	Thomson NC Patel M Smith AD
author_sort	Thomson NC
title	Lebrikizumab in the personalized management of asthma
title_short	Lebrikizumab in the personalized management of asthma
title_full	Lebrikizumab in the personalized management of asthma
title_fullStr	Lebrikizumab in the personalized management of asthma
title_full_unstemmed	Lebrikizumab in the personalized management of asthma
title_sort	lebrikizumab in the personalized management of asthma
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/cee825f901ba45e4abab67fd7204c126
work_keys_str_mv	AT thomsonnc lebrikizumabinthepersonalizedmanagementofasthma AT patelm lebrikizumabinthepersonalizedmanagementofasthma AT smithad lebrikizumabinthepersonalizedmanagementofasthma
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Lebrikizumab in the personalized management of asthma

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