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分层医学在选择生物制剂治疗严重哮喘中的应用。

Stratified medicine in selecting biologics for the treatment of severe asthma.

机构信息

IIR Division, School of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK.

出版信息

Curr Opin Allergy Clin Immunol. 2011 Feb;11(1):58-63. doi: 10.1097/ACI.0b013e3283423245.

Abstract

PURPOSE OF REVIEW

Despite optimal treatment, asthma symptoms in about 5-10% of patients remain poorly controlled. Apart from having an impact on their asthma-related quality of life and adverse effects of the medications used (especially corticosteroids), their severe symptoms also impact healthcare resources due to frequent admission and requirement for intensive medications use. The last decade has seen an improved understanding in the pathophysiology of the complex cellular and molecular networks involved in the inflammatory and immunological phenotype of severe asthma. This knowledge may help providing strategies by which these phenotypes operate and pave the way for drug development and individualized treatment.

RECENT FINDINGS

Here we review the current evidence of biological agents in patients with severe asthma recently assessed for safety and efficacy. Some of these agents have shown to be useful in specifically targeted subpopulations of patients with severe asthma, whereas others have proven to be unsafe and/or unsuccessful. In addition, we discuss recent data on clinical and pharmacokinetic-pharmacodynamic aspects of omalizumab, the only licensed anti-IgE therapy for severe atopic asthma.

SUMMARY

More basic science work is required to improve the current understanding of severe asthma pathophysiology and proof-of-concept clinical studies are required to explore relevant biomolecular targets in this small subset of patients. At present, only one drug is licensed for allergic asthmatic patients with severe disease, omalizumab. Novel therapies in the form of oligonucleotide therapies and other biological agents are also being investigated in the difficult-to-treat asthmatic patient group.

摘要

目的综述

尽管采用了最佳治疗方法,但仍有约 5-10%的哮喘患者的症状控制不佳。除了对哮喘相关生活质量和所用药物(尤其是皮质类固醇)的不良反应产生影响外,这些患者的严重症状还因频繁住院和需要强化药物治疗而对医疗资源产生影响。在过去的十年中,人们对严重哮喘炎症和免疫表型所涉及的复杂细胞和分子网络的病理生理学有了更深入的了解。这一知识可能有助于提供了解这些表型作用的策略,并为药物开发和个体化治疗铺平道路。

最新发现

本文综述了最近评估安全性和疗效的严重哮喘患者中生物制剂的现有证据。其中一些药物已被证明对严重哮喘的特定靶向亚群患者有用,而另一些则被证明不安全和/或无效。此外,我们还讨论了奥马珠单抗的临床和药代动力学-药效学方面的最新数据,奥马珠单抗是唯一获准用于严重特应性哮喘的抗 IgE 治疗药物。

总结

需要更多的基础科学工作来提高对严重哮喘病理生理学的现有认识,需要进行概念验证的临床研究来探索这一小部分患者中的相关生物分子靶点。目前,只有一种药物奥马珠单抗被批准用于严重疾病的过敏性哮喘患者。新型疗法,如寡核苷酸疗法和其他生物制剂,也正在针对难以治疗的哮喘患者群体进行研究。

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