文献简介

出版社:Nature reviews

作  者:

编  号:

关键字:系统性红斑狼疮;新疗法

年  份:2019   点击量:1

文献摘要 全文翻译

The failure of many new , mostly biologic, drugs to meet their primary end points in double- blind clinical trials in patients with systemic lupus erythematosus (SLE) has caused a profound sense of disappointment among both physicians and patients. Arguably , the success of B cell depletion with rituximab in open-label clinical trials, the approval of belimumab (which blocks B cell- activating factor (BAFF)) for use in patients with lupus nephritis in the USA and in difficult- to-treat patients with SLE in the UK and the recognition that clinical trial design can be improved have given some cause for hope. However, changes to therapies in current use and the development of new approaches are urgently needed. The results of the latest studies investigating the use of several new approaches to treating SLE are discussed in this Review , including: fully humanized anti-CD20 and anti-CD19 monoclonal antibodies; inhibition of tyrosine-protein kinase BTK; CD40 ligand blockade; interfering with the presentation of antigen to autoreactive T cells using a peptide approach; a receptor decoy approach using an analogue of Fcγ receptor IIB; dual blockade of IL-12 and IL-23; and inhibition of Janus kinases.

在对系统性红斑狼疮(SLE)患者进行的双盲临床试验中,许多新药物(主要是生物制剂)未能达到其主要终点,这使医生和患者都深感失望可以说,利妥昔单抗在开放性研究中、在美国狼疮肾炎患者和在英国难以治疗的系统性红斑狼疮患者中成功地消除了B细胞,以及贝利马单抗(阻断B细胞活化因子)被批准用于系统性红斑狼疮患者,并认识到临床试验设计可以改进,给人们带来了希望。然而,迫切需要改变当前疗法和开发新的方法。本综述讨论了使用几种新疗法治疗SLE的最新研究结果,包括:人源化抗CD20和抗CD19单克隆抗体;以及酪氨酸蛋白激酶BTK的抑制CD40配体阻断;使用肽方法干扰抗原向自身反应性T细胞呈递; 使用Fcγ受体IIB类似物的受体引诱方法;IL-12IL-23双重阻断;和抑制Janus激酶。