Editorial: [Monoclonal Antibodies in the Treatment of Asthma(Guest Editor: Moshe Ben-Shoshan)]

E-ISSN： 2212-2710|4|3|180-182

ISSN： 1872-213X

Source： Recent Patents on Inflammation & Allergy Drug Discovery, Vol.4, Iss.3, 2010-11, pp. : 180-182

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

Asthma is a chronic inflammatory disorder of the airway in which many cells play a role. The inflammation results in recurrent coughing, breathless, chest tightness and airway obstruction often reversible [1].The use of inhaled corticosteroids, short and long acting beta2-adrenoceptor agonists and inhibitors of leukotrienes provide most asthmatic patients with good disease control. However, none of these therapies are specifically directed to the underlying causal pathways of asthma. Further, almost 10%of asthma patients have severe asthma that is often steroid-resistant [2-4]. These patients are responsible for more than 50% of health care expenditure for all asthma due to the lack of appropriate pharmacological therapy[5].Recent studies suggest that asthma is a heterogeneous disorder presenting with many phenotypes. These phenotypes are likely the result of specific gene- environment interactions and are defined by many interacting factors including: age of patients, age of disease onset, corticosteroid resistance, chronic airflow obstruction, and evidence for eosinophilic airway inflammation on biopsy [6,7]. Therapies based on phenotypic and genotypic characteristics may be useful in asthma management and contribute to better asthma control potentially also in those that are relatively treatment resistant [8,9]. It is also possible that while current asthma treatments were not shown to affect the natural course of asthma, treatment tailored to a specific phenotype may have such an effect. Indeed, monoclonal antibodies affect specific immunologic pathways involved in asthma pathogenesis and recent studies suggest specific benefits of certain monoclonal antibodies in different asthma phenotypes. Thus, monoclonal antibodies tailored therapies to asthma may well provide the future biologic modifiers of asthma and be used as second or even first line of personalized asthma treatment. In this monothematic issue we sought to describe monoclonal antibodies with potential role in asthma treatment and to highlight key issues related to their mechanisms of action, potential contribution to asthma treatment as well as side effects and future directions related to pertinent patents. Monoclonal antibodies discussed include: anti-IgE, anti-Tumor Necrosis Factor (TNF) anti-Interleukin 5 (IL5), anti-integrins, anti-CD25 and anti-Th2 cytokines.Omalizumab is currently the only IgE-targeted therapy approved by the United States Food and Drug Administration for asthma treatment. It is used in patients with inadequately controlled moderate-to-severe persistent allergic asthma that is not controlled with high-dose inhaled corticosteroids [10]. The PERSIST study as well as other recent studies suggest that under real-life conditions, omalizumab is effective as add-on therapy in the treatment of patients with persistent severe allergic asthma including steroid-resistant asthma [11,12]. Further, as discussed in this issue, its potential off label use in asthma e.g. in children and in asthma related diseases suggests future broader applications. Although current studies suggest acceptable safety profile future studies exploring the long term consequences of omalizumab treatment are still required.Another family of monoclonal antibodies with a possible role in asthma treatment targets the TNF axis. Preliminary studies have demonstrated an improvement in asthma quality of life, lung function, airway hyperresponsiveness and a reduction in exacerbation frequency in patients treated with anti-TNF-alpha therapy. However, there is marked heterogeneity in response and anti-TNF treatment may benefit mainly a specific subset of asthma in which TNF may play a crucial pathogenic role [13]. As discussed in this issue by Dr. Desai and Prof. Brightling this subgroup may consist mainly of those with late onset disease. Given the risk for severe infections and malignancy risk associated with anti-TNF treatment, the safety profile of anti-TNF treatment remains at this

Abstract

Related content