利妥昔单抗在风湿性疾病中的当前观点。
Current perspective on rituximab in rheumatic diseases.
作者信息
Schioppo Tommaso, Ingegnoli Francesca
机构信息
Department of Clinical Sciences and Community Health, Division of Rheumatology, ASST Pini, Università degli Studi di Milano, Milano, Italy.
出版信息
Drug Des Devel Ther. 2017 Oct 3;11:2891-2904. doi: 10.2147/DDDT.S139248. eCollection 2017.
The steadily increasing knowledge regarding pathogenetic mechanisms in autoimmune rheumatic diseases has paved the way to different therapeutic approaches. In particular, the market entry of biologics has dramatically modified the natural history of rheumatic chronic inflammatory diseases with a meaningful impact on patients' quality of life. Among the wide spectrum of available biological treatments, rituximab (RTX), first used in the treatment of non-Hodgkin's lymphoma, was later approved for rheumatoid arthritis and anti-neutrophil cytoplasmic antibodies-associated vasculitis. Nowadays, in rheumatology, RTX is also used with off-label indications in patients with systemic sclerosis, Sjögren's syndrome and systemic lupus erythematosus. RTX is a monoclonal antibody directed to CD20 molecules expressed on the surfaces of pre-B and mature B lymphocytes. It acts by causing apoptosis of these cells with antibody- and complement-dependent cytotoxicity. As inflammatory responses to cell-associated immune complexes are key elements in the pathogenesis of several autoimmune rheumatic diseases, such an approach might be effective in these patients. In fact, RTX, by promoting the rapid and long-term depletion of circulating and lymphoid tissue-associated B cells, leads to a lower recruitment of these effector cells at sites of immune complex deposition, thus reducing inflammation and tissue damage. RTX is of the most interest to rheumatologists as it represents an important additional therapeutic approach. Thus, the advent in clinical practice of approved RTX biosimilars, such as CT-P10, may be of help in improving treatment access as well as in reducing costs.
关于自身免疫性风湿性疾病发病机制的知识不断增加,为不同的治疗方法铺平了道路。特别是,生物制剂进入市场极大地改变了风湿性慢性炎症性疾病的自然病程,对患者的生活质量产生了重大影响。在广泛可用的生物治疗方法中,利妥昔单抗(RTX)最初用于治疗非霍奇金淋巴瘤,后来被批准用于治疗类风湿性关节炎和抗中性粒细胞胞浆抗体相关血管炎。如今,在风湿病学中,RTX也被用于系统性硬化症、干燥综合征和系统性红斑狼疮患者的非标签适应症。RTX是一种针对前B淋巴细胞和成熟B淋巴细胞表面表达的CD20分子的单克隆抗体。它通过抗体和补体依赖性细胞毒性导致这些细胞凋亡而起作用。由于对细胞相关免疫复合物的炎症反应是几种自身免疫性风湿性疾病发病机制中的关键因素,这种方法可能对这些患者有效。事实上,RTX通过促进循环和淋巴组织相关B细胞的快速和长期耗竭,导致这些效应细胞在免疫复合物沉积部位的募集减少,从而减轻炎症和组织损伤。RTX是风湿病学家最感兴趣的药物,因为它代表了一种重要的额外治疗方法。因此,批准的RTX生物类似药(如CT-P10)在临床实践中的出现可能有助于改善治疗的可及性并降低成本。