Masitinib, a c‐kit/PDGF receptor tyrosine kinase inhibitor, improves disease control in severe corticosteroid‐dependent asthmatics

Humbert, Marc; Blay, F. De; Garcia, Gilles; Prudhomme, A.; Leroyer, Christophe; Magnan, A.; Tunon-de-Lara, José-Manuel; Pison, Christophe; Aubier, Michel; Charpin, D; Vachier, Isabelle; Purohit, Ahl; Gineste, Paul; Bader, Thomas; Moussy, A.; Hermine, Olivier; Chanez, Pascal

doi:10.1111/j.1398-9995.2009.02122.x

Cited by 131 publications

(97 citation statements)

References 23 publications

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“…A tyrosine kinase inhibitor, masitinib, which targets stem cell factor receptor and platelet-derived growth factor improved asthma control in adults when compared with placebo in the face of a reducing dose of OCS; however, there was no effect on lung function [161]. Daclizumab, a humanised IgG1 monoclonal antibody against the IL-2 receptor-a chain of activated lymphocytes improved FEV1 and asthma control in moderate-to-severe asthmatic adults inadequately controlled on ICS [162].…”

Section: Remarksmentioning

confidence: 99%

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: Remarksmentioning

confidence: 99%

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

et al. 2013

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“…A specific ckit tyrosine kinase inhibitor imatinib inhibits hyperresponsiveness, inflammation and remodeling in murine asthma models [126] and is undergoing clinical trial evaluation in severe refractory asthma (ClinicalTrials.gov Identifier: NCT01097694). A tyrosine kinase inhibitor masitinib that targets c-kit and the platelet-derived growth factor (PDGF) receptor improved asthma control in patients with severe corticosteroid-dependent asthma [127] and a further clinical trial is underway in patients with severe persistent asthma treated with oral corticosteroids (ClinicalTrials.gov Identifier: NCT01449162).…”

Section: Macrolidesmentioning

confidence: 99%

Addressing corticosteroid insensitivity in adults with asthma

Thomson

2016

Expert Review of Respiratory Medicine

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Corticosteroids are the most effective treatment for asthma, but the therapeutic response varies markedly between individuals, with up to one third of patients showing evidence of insensitivity to corticosteroids. This article summarizes information on genetic, environmental and asthma-related factors as well as demographic and pharmacokinetic variables associated with corticosteroid insensitivity in asthma. Molecular mechanisms proposed to explain corticosteroid insensitivity are reviewed including alterations in glucocorticoid receptor subtype, binding and nuclear translocation, increased proinflammatory transcription factors and defective histone acetylation. Current therapies and future interventions that may restore corticosteroid sensitivity in asthma are discussed, including small molecule drugs and biological agents. In the future, biomarkers may be used in the clinic to predict corticosteroid sensitivity in patients with poorly controlled asthma. Word count: 120 wordsKey words: Adherence; asthma; biological agents; biomarkers; cigarette smoking; corticosteroids; corticosteroid insensitivity; corticosteroid resistance; small molecule drugs. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 IntroductionAsthma is a chronic inflammatory disease of the airways that affects 300 million people worldwide. Both national and international guidelines recommend daily inhaled corticosteroid as the preferred controller treatment for adults and adolescents with asthma who have poor symptom control or who at risk of exacerbations [201, 202]. Inhaled corticosteroid use in asthma reduces symptoms, improves quality of life and increases lung function as well as decreases the rate of exacerbations [201, 202]. The majority of the therapeutic benefits of inhaled corticosteroids are achieved at low to medium doses [1], although higher doses are often required in patients with more severe asthma [2] [202]. Short courses of oral corticosteroids are administered to treat severe exacerbations and daily oral corticosteroids are used in the lowest dose providing adequate control to treat patients with severe asthma when symptoms are uncontrolled despite maximal therapy [201, 202].Guideline recommendations for inhaled and oral corticosteroid use in asthma are based on average therapeutic responses from clinical trial populations that may not be representative of 'real-life' patients [3]. Numerous studies in adults and children with asthma have noted a considerable patient-to-patient variability in improvements in lung function and airway hyperreactivity with inhaled and oral corticosteroid treatment in patients with apparently similar levels of disease severity [4][5][6] (Figure 1). The findings from these studies suggest that corticosteroid insensitivity may be present in approximately one third of patients with asthma.Inhaled corticosteroids exhib...

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“…Masitinib is a potent blocker of c-Kit and provides some symptomatic benefit in patients with severe asthma. More selective c-Kit inhibitors are in development (Humbert et al, 2009).…”

Section: Mast Cell Inhibitorsmentioning

confidence: 99%

An Overview and Update on Asthma and its Management

Rajanandh¹

2015

J. of Medical Sciences

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Masitinib, a c‐kit/PDGF receptor tyrosine kinase inhibitor, improves disease control in severe corticosteroid‐dependent asthmatics

Abstract: Masitinib, a c-kit and PDGF-receptor tyrosine kinase inhibitor, may represent an innovative avenue of treatment in corticosteroid-dependent asthma. These preliminary results warrant further long-term clinical studies in severe asthma

Cited by 131 publications

References 23 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

Addressing corticosteroid insensitivity in adults with asthma

An Overview and Update on Asthma and its Management

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