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哮喘的未来生物疗法。

Future biologic therapies in asthma.

机构信息

Servicio de Alergología, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, España.

Servicio de Alergología, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, España.

出版信息

Arch Bronconeumol. 2014 Aug;50(8):355-61. doi: 10.1016/j.arbres.2014.02.002. Epub 2014 Mar 29.

DOI:10.1016/j.arbres.2014.02.002
PMID:24685200
Abstract

Despite the administration of appropriate treatment, a high number of patients with asthma remain uncontrolled. This suggests the need for alternative treatments that are effective, safe and selective for the established asthma phenotypes, especially in patients with uncontrolled severe asthma. The most promising options among the new asthma treatments in development are biological therapies, particularly those monoclonal antibodies directed at selective targets. It should be noted that the different drugs, and especially the new biologics, act on very specific pathogenic pathways. Therefore, determination of the individual profile of predominant pathophysiological alterations of each patient will be increasingly important for prescribing the most appropriate treatment in each case. The treatment of severe allergic asthma with anti-IgE monoclonal antibody (omalizumab) has been shown to be effective in a large number of patients, and new anti-IgE antibodies with improved pharmacodynamic properties are being investigated. Among developing therapies, biologics designed to block certain pro-inflammatory cytokines, such as IL-5 (mepolizumab) and IL-13 (lebrikizumab), have a greater chance of being used in the clinic. Perhaps blocking more than one cytokine pathway (such as IL-4 and IL-13 with dulipumab) might confer increased efficacy of treatment, along with acceptable safety. Stratification of asthma based on the predominant pathogenic mechanisms of each patient (phenoendotypes) is slowly, but probably irreversibly, emerging as a tailored medical approach to asthma, and is becoming a key factor in the development of drugs for this complex respiratory syndrome.

摘要

尽管给予了适当的治疗,仍有大量哮喘患者的病情得不到控制。这表明需要寻找其他有效的、安全的且针对已确定的哮喘表型的治疗方法,尤其是对那些控制不佳的重度哮喘患者。在开发中的新型哮喘治疗中,最有前景的选择是生物疗法,特别是针对特定靶点的单克隆抗体。需要注意的是,不同的药物,尤其是新型生物制剂,作用于非常特定的致病途径。因此,对于每位患者,确定其主要病理生理改变的个体特征将变得越来越重要,这有助于为每个患者选择最合适的治疗方法。抗 IgE 单克隆抗体(奥马珠单抗)治疗重度过敏性哮喘在大量患者中已被证实有效,且正在研究具有改善药效学特性的新型抗 IgE 抗体。在开发中的治疗方法中,旨在阻断某些促炎细胞因子(如 IL-5(美泊利单抗)和 IL-13(利匹鲁单抗))的生物制剂更有可能在临床上得到应用。或许阻断多个细胞因子途径(如用度普利尤单抗阻断 IL-4 和 IL-13)可能会提高治疗效果,同时保持可接受的安全性。基于每位患者的主要致病机制(表型)对哮喘进行分层(表型分类)正缓慢但可能不可逆转地成为一种针对哮喘的个体化医疗方法,并成为开发这种复杂呼吸系统综合征药物的关键因素。

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