系统性红斑狼疮的靶向治疗药物研究进展

Advances in targeted therapeutic agents for systemic lupus erythematosus

目前系统性红斑狼疮(systemic lupus erythematosus,SLE)的治疗仍主要依赖糖皮质激素和免疫抑制剂,治疗现状并不令人满意,部分患者对这些传统治疗药物反应不佳,同时存在治疗相关不良反应,因此需要治疗SLE的新型药物。而SLE发病机制的复杂性给新药研发带来了挑战。近年来,随着对SLE发病机制认识的不断深入,针对SLE发病机制中各种不同靶点的药物层出不穷,其中靶向B细胞的贝利尤单抗、泰它西普已在我国获批用于SLE的治疗,还有多种靶向治疗新药处在Ⅱ期或Ⅲ期临床试验阶段。本文通过汇总针对B细胞/浆细胞、Ⅰ型干扰素、共刺激因子、Janus激酶/信号转导与转录激活因子(JAK/STAT)通路、布鲁顿氏酪氨酸激酶、细胞因子等相关靶向药物在SLE中的临床研究现状,以期为国内风湿科医师提供最新的信息。

At present,the treatment of systemic lupus erythematosus(SLE)still mainly relies on glucocorticoids and immunosuppressants,and the treatment status is unsatisfactory.Some patients poorly respond to these traditional therapeutic agents,along with treatment-related adverse effects,which makes novel drugs for treating SLE needed,but the complexity of the pathogenesis of SLE poses a challenge to new drug development.Various new targets for treatment have been discovered from recent advances of SLE pathogenesis in our understanding.Belimumab and telitacicep,which target B cells,have been approved for SLE treatment in China.Multiple new targeted herapeutics drugs are in phase Ⅱ or phase Ⅲ clinical trials.In this review,we provide an update on current research findings of targeted drugs,which target B cells/plasma cells,type Ⅰ interferon,costimulators,JAK/STAT pathway,Bruton tyrosine kinase,and cytokines,hoping to provide the new information for rheumatologists.