Centre for Rheumatology and Connective Tissue Diseases, UCL Medical School, Royal Free Hospital, London, UK.
Curr Opin Rheumatol. 2010 May;22(3):264-72. doi: 10.1097/BOR.0b013e328337c3d6.
The purpose of this study is to review the evidence and recent developments leading to novel therapeutics in scleroderma.
Recent advances have been made in understanding the key pathogenetic aspects of scleroderma, and these have led to potential targeted therapeutic agents for the management of these patients. Preliminary data from early clinical trials suggest that tyrosine kinase molecules may be potential candidates for therapy, especially in the fibrotic phase of the disease. On the basis of the new insights into the key role of effector T cells, in particular Th-17 and T regulatory subsets, T-cell-directed therapies including halofuginone, basiliximab, alemtuzumab, abatacept and rapamycin have been proposed to be clinically beneficial. By analogy, recent clinical studies with rituximab in diffuse cutaneous systemic sclerosis lend support that B cells may be important in the pathogenesis of the disease. 3-Hydroxy-3-methyl-glutaryl-CoA reductase inhibitors, endothelin receptor antagonists and phosphodiesterase type V inhibitor have been shown to be useful to treat the vascular manifestations associated with systemic sclerosis. Haematopoietic stem cell transplantation following immune ablation holds considerable promise in resetting of the immune system, and trial results are awaited.
Although there is still no treatment that is unequivocally effective for scleroderma, there have been some promising developments over the past number of years with identification of novel candidate targets and innovative strategies, including targeted immunomodulatory therapies, tyrosine kinase inhibitors and agents that may promote vascular repair. These recent findings will need to be confirmed by larger, multicentre, randomized controlled trials, but they provide hope that these novel therapeutic agents may broaden the currently restricted therapeutic armamentarium of the disease.
本研究旨在综述硬皮病新疗法的相关证据和最新进展。
人们对硬皮病发病机制的关键方面的认识取得了新进展，这为这些患者的治疗带来了潜在的靶向治疗药物。早期临床试验的初步数据表明，酪氨酸激酶分子可能是治疗的潜在候选药物，特别是在疾病的纤维化阶段。基于对效应 T 细胞（特别是 Th-17 和 T 调节亚群）关键作用的新认识，包括 halofuginone、巴利昔单抗、阿仑单抗、abatacept 和雷帕霉素在内的 T 细胞靶向治疗被提出可能具有临床益处。类似地，最近弥漫性皮肤系统性硬皮病的利妥昔单抗临床研究支持 B 细胞在疾病发病机制中可能很重要。3-羟基-3-甲基戊二酰辅酶 A 还原酶抑制剂、内皮素受体拮抗剂和磷酸二酯酶 5 抑制剂已被证明可有效治疗与系统性硬皮病相关的血管表现。免疫清除后造血干细胞移植在重置免疫系统方面具有很大的潜力，正在等待试验结果。
尽管目前还没有治疗硬皮病的方法是绝对有效的，但在过去几年中，通过确定新的候选靶点和创新策略，包括靶向免疫调节疗法、酪氨酸激酶抑制剂和可能促进血管修复的药物，取得了一些有希望的进展。这些新发现需要通过更大规模、多中心、随机对照试验来证实，但它们为这些新型治疗药物可能拓宽目前对该疾病有限的治疗手段提供了希望。
