Reslizumab for Poorly Controlled, Eosinophilic Asthma

Castro, Mario; Mathur, Sameer K.; Hargreave, Frederick E.; Boulet, Louis‐Philippe; Xie, Fang; Young, James B.; Wilkins, Hannah; Henkel, Tim; Nair, Parameswaran

doi:10.1164/rccm.201103-0396oc

Cited by 652 publications

(456 citation statements)

References 24 publications

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“…2) [54,55]. Eosinophilic inflammation, for instance, is likely to have a Th2 immune component, a reflection of adaptive immunity, as evidenced by four separate studies demonstrating efficacy of a monoclonal antibody to IL-5 in eosinophilic severe asthma in adults [14,[56][57][58]. Whether the Th2 profile is similar to that observed in corticosteroid-naïve patients awaits further study, but would be supported by studies demonstrating efficacy of an anti-IL-13 antibody in improving FEV1 in adult patients with moderate-to-severe asthma [59,60].…”

Section: Inflammation and Adaptive Immunitymentioning

confidence: 99%

“…While the anti-IL5 antibody, mepolizumab, was not beneficial in unselected adult patients with moderate asthma [222], when studied in severe asthma patients with persistent sputum eosinophilia, two anti-IL-5 antibodies, mepolizumab and reslizumab, have been shown to decrease exacerbations and OCS use, as well as improve symptoms and lung function to varying degrees [57,58,157]. A larger study with mepolizumab showed efficacy in adults and adolescents solely in terms of a reduction in exacerbation rate, without improvement in FEV1 and quality of life [56].…”

Section: Remarksmentioning

confidence: 99%

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International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

et al. 2013

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Severe or therapy-resistant asthma is increasingly recognised as a major unmet need. A Task Force, supported by the European Respiratory Society and American Thoracic Society, reviewed the definition and provided recommendations and guidelines on the evaluation and treatment of severe asthma in children and adults.A literature review was performed, followed by discussion by an expert committee according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for development of specific clinical recommendations.When the diagnosis of asthma is confirmed and comorbidities addressed, severe asthma is defined as asthma that requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming “uncontrolled” or that remains “uncontrolled” despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma. Specific recommendations on the use of sputum eosinophil count and exhaled nitric oxide to guide therapy, as well as treatment with anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty are provided.Coordinated research efforts for improved phenotyping will provide safe and effective biomarker-driven approaches to severe asthma therapy.

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Section: Inflammation and Adaptive Immunitymentioning

confidence: 99%

Section: Remarksmentioning

confidence: 99%

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

et al. 2013

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“…Клинически при при-менении меполизумаба отмечалось снижение частоты обострений БА, улучшение качества жизни без улучшения функции дыхательных путей и снижения гиперреактив-ности бронхов [31]. Апробация другого препарата, ней-трализующего IL5, -реслизумаба (reslizumab) в рандо-мизированном плацебоконтролируемом исследовании показала его положительное влияние на контроль астмы, документированный улучшением показателя ОФВ 1 , что, по мнению исследователей, подтверждало влияние эози-нофилов на течение БА и ее исходы [32].…”

Section: моноклональные антителаunclassified

Potential Role of Serum Periostin in the Early Detection of Bronchial Asthma in Children

Sobotyuk¹,

Gaponenko²,

Бочанцев³

et al. 2016

Vopr. sovr. pediatr.

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АКТУАЛЬНОСТЬНи значительные достижения в диагностике бронхи-альной астмы (БА), ни внедрение в практику современных методов контроля и профилактики бронхиальной обструк-ции так и не привели к снижению заболеваемости, осо-бенно среди детского населения. B наши дни БА -наи-более распространенная хроническая форма патологии дыхательных путей в младшей возрастной группе [1,2].В конце XX -начале XXI века исследователи на экс-периментальных моделях убедительно показали, что Т хел перы второго типа (Th2) играют важнейшую роль в развитии аллергической БА, и с их активацией связаны

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“…Agents such as anti-IL-4 mAb, anti-IL-5 mAb, and anti-CCR3 mAb blocked the formation of airway inflammation in animal models of asthma, but failed in clinical trials (Antoniu, 2009;Busse et al, 2010;Corren et al, 2010;Castro et al, 2011;Pavord et al, 2012). It is likely that in preclinical studies, these agents were effective as preventative therapy, but not necessarily able to reverse established disease.…”

Section: Fig 6 Effect Of Anti-cd69 Mab On Ova-induced Ahrmentioning

confidence: 99%

Anti-CD69 monoclonal antibody treatment inhibits airway inflammation in a mouse model of asthma

Wang

Dai

Wang

et al. 2015

J. Zhejiang Univ. Sci. B

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Abstract:Objective: Airway inflammation and airway hyper-responsiveness (AHR) are principle pathological manifestations of asthma. Cluster of differentiation 69 (CD69) is a well-known co-stimulatory factor associated with the activation, proliferation as well as apoptosis of immune cells. This study aims to examine the effect of anti-CD69 monoclonal antibody (mAb) on the pathophysiology of a mouse model of asthma. Methods: A murine model of ovalbumin (OVA)-induced allergic airway inflammation was used in this study. Briefly, mice were injected with 20 μg chicken OVA intraperitoneally on Days 0 and 14, followed by aerosol provocation with 1% (0.01 g/ml) OVA on Days 24, 25, and 26. Anti-CD69 mAb or isotype IgG was injected intraperitoneally after OVA challenge; dexamethasone (DXM) was administrated either before or after OVA challenge. AHR, mucus production, and eosinophil infiltration in the peribronchial area were examined. The levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-5 (IL-5) in bronchoalveolar lavage fluid (BALF) were also assayed as indices of airway inflammation on Day 28 following OVA injection. Results: Pretreatment with DXM together with anti-CD69 mAb treatment after OVA provocation completely inhibited AHR, eosinophil infiltration and mucus overproduction, and significantly reduced BALF IL-5. However, treatment with DXM alone after OVA challenge only partially inhibited AHR, eosinophil infiltration and mucus overproduction, and did not diminish BALF IL-5. Treatment with either DXM or anti-CD69 mAb did not alter the concentration of BALF GM-CSF. Conclusions: Anti-CD69 mAb treatment inhibits established airway inflammation as effectively as DXM pretreatment. This study provides a potential alternative therapeutic opportunity for the clinical management of asthma and its exacerbation.

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Reslizumab for Poorly Controlled, Eosinophilic Asthma

Abstract: Patients receiving reslizumab showed significantly greater reductions in sputum eosinophils, improvements in airway function, and a trend toward greater asthma control than those receiving placebo. Reslizumab was generally well tolerated.

Cited by 652 publications

References 24 publications

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

Potential Role of Serum Periostin in the Early Detection of Bronchial Asthma in Children

Anti-CD69 monoclonal antibody treatment inhibits airway inflammation in a mouse model of asthma

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