Hanaoka Hironari, Takeuchi Tsutomu
Division of Rheumatology, Department of Internal Medicine Keio University School of Medicine.
Nihon Rinsho Meneki Gakkai Kaishi. 2013;36(4):181-8. doi: 10.2177/jsci.36.181.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies to various cellular components. Although many of therapies have shown great efficacy, they often associate with adverse effects. The development of safer therapies for SLE has led to recent emphasis on targeting selected pathways that can be important in the inflammatory process in SLE. The cytokine family of type I interferons (IFNs), and especially the IFNα subtypes, are implicated in pathogenesis of SLE. Genetic polymorphisms of several components of the IFN signaling pathway have been associated with an increased risk of SLE. Therefore, IFNα subtypes have been identified as a potential target for drug development in SLE. There have been developed three agents, IFNα-targeted therapy, Sifalimumab, Rontalizumab and NNC 0152-0000-0001. They are anti-IFNα monoclonal antibodies that bind to and specifically neutralizes most IFNα subtypes, preventing signaling through the type I IFN receptor. The safety and dose-proportional pharmacokinetics of those agents were demonstrated. A larger study is currently ongoing, further safety profile will be evaluated. This review provides an update on the ongoing clinical trials of anti-IFNα therapy and the promise and obstacles in the use of biologics in SLE.
系统性红斑狼疮（SLE）是一种全身性自身免疫性疾病，其特征是针对各种细胞成分产生自身抗体。尽管许多疗法已显示出显著疗效，但它们常常伴有不良反应。开发更安全的SLE疗法促使近期人们将重点放在靶向某些在SLE炎症过程中可能起重要作用的特定途径上。I型干扰素（IFN）细胞因子家族，尤其是IFNα亚型，与SLE的发病机制有关。IFN信号通路的几个成分的基因多态性与SLE风险增加有关。因此，IFNα亚型已被确定为SLE药物开发的一个潜在靶点。已经开发出三种药物，即IFNα靶向疗法、西法昔单抗、罗坦珠单抗和NNC 0152 - 0000 - 0001。它们是抗IFNα单克隆抗体，可结合并特异性中和大多数IFNα亚型，阻止通过I型IFN受体的信号传导。已证实这些药物的安全性和剂量比例药代动力学。目前正在进行一项更大规模的研究，将进一步评估其安全性。本综述提供了抗IFNα疗法正在进行的临床试验的最新情况，以及在SLE中使用生物制剂的前景和障碍。
