Department of Rheumatology, Cork University Hospital, Cork, Ireland.
Centre for Rheumatology/Division of Medicine, University College London, London, UK.
Nat Rev Rheumatol. 2019 Jul;15(7):403-412. doi: 10.1038/s41584-019-0235-5.
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.
在系统性红斑狼疮（SLE）患者的双盲临床试验中，许多新型药物（主要为生物制剂）未能达到主要终点，这给医生和患者都带来了极大的失望。可以说，利妥昔单抗（rituximab）在开放标签临床试验中的 B 细胞耗竭取得了成功，贝利尤单抗（belimumab，可阻断 B 细胞激活因子（BAFF））在美国狼疮肾炎患者和英国难治性 SLE 患者中的获批，以及临床试验设计可以得到改善，这些都给人带来了一线希望。然而，迫切需要改变当前使用的治疗方法并开发新的方法。本综述讨论了几项治疗 SLE 的新方法的最新研究结果，包括：完全人源化抗 CD20 和抗 CD19 单克隆抗体；抑制酪氨酸蛋白激酶 BTK；CD40 配体阻断；使用肽方法干扰抗原呈递给自身反应性 T 细胞；使用 Fcγ 受体 IIB 类似物的受体诱饵方法；阻断白细胞介素-12 和白细胞介素-23 的双重阻断；以及抑制 Janus 激酶。
