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贝利尤单抗治疗系统性红斑狼疮的临床试验综述

A Review of Clinical Trials of Belimumab in the Management of Systemic Lupus Erythematosus.

作者信息

Garcia Alexis, De Sanctis Juan B

机构信息

Instituto de Inmunología, Facultad de Medicina, Universidad Central de Venezuela, Apartado 50109, Caracas 1050-A, Venezuela.

出版信息

Curr Pharm Des. 2016;22(41):6306-6312. doi: 10.2174/1381612822666160831103254.

Abstract

There have been few changes over the last 50 years in the treatment of Systemic lupus erythematosus (SLE), using non-specific anti-inflammatory agents such as: nonsteroidal anti-inflammatory drugs along with the immune cell modulating agent hydroxychloroquine for mild disease, and broad spectrum immunosuppressants plus antiinflammatories such as corticosteroids, azathioprine, cyclophosphamide, or mycophenolate during flares or severe disease with organ involvement. In some patients, the response is inadequate and side effects appear from mild unpleasant up to severe toxicity. Drug metabolism and clearance may be severely compromised. Therefore, it is a priority to develop better treatments with fewer adverse events that can be used at different stages of disease activity. In recent years, a member of the tumor necrosis factor (TNF) family, soluble human B Lymphocyte Stimulator protein (BLyS), also referred to as B-cell activating factor (BAFF) and TNFSF13B has been studied extensively. This protein is synthesized by myeloid cell lines, specifically interacts with B lymphocytes and increases their life-span. BlyS plays a key role in the selection, maturation and survival of B cells and it has a significant role in the pathogenesis of SLE. In this review, we analyzed the role of BLyS as a diagnostic/prognostic marker and/or therapeutic target for lupus patients, and the different clinical studies published using belimumab.

摘要

在过去50年里,系统性红斑狼疮(SLE)的治疗方法变化不大,对于轻症患者,使用非特异性抗炎药,如非甾体抗炎药,同时联合免疫细胞调节剂羟氯喹;对于病情发作或累及器官的重症患者,则使用广谱免疫抑制剂加抗炎药,如皮质类固醇、硫唑嘌呤、环磷酰胺或霉酚酸酯。在一些患者中,治疗反应欠佳,且会出现从轻微不适到严重毒性的副作用。药物代谢和清除可能会严重受损。因此,开发更好的、不良事件较少且可在疾病活动的不同阶段使用的治疗方法成为当务之急。近年来,肿瘤坏死因子(TNF)家族的成员可溶性人B淋巴细胞刺激蛋白(BLyS),也被称为B细胞活化因子(BAFF)和TNFSF13B,受到了广泛研究。这种蛋白由髓系细胞系合成,特异性地与B淋巴细胞相互作用并延长其寿命。BLyS在B细胞的选择、成熟和存活中起关键作用,并且在SLE的发病机制中具有重要作用。在本综述中,我们分析了BLyS作为狼疮患者诊断/预后标志物和/或治疗靶点的作用,以及使用贝利尤单抗发表的不同临床研究。

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