Rituximab for the treatment of rheumatoid arthritis: an update.
Rituximab for the treatment of rheumatoid arthritis: an update.
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DOI：
10.2147/dddt.s41645
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发表时间：
2013-12-27
期刊：
影响因子：
--
通讯作者：
Mok CC
中科院分区：
文献类型：
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作者：
Mok CC
利妥昔单抗是一种嵌合单克隆抗体，靶向B细胞表面表达的CD20分子。它最初用于治疗非霍奇金淋巴瘤，后来被批准用于治疗对疾病缓解抗风湿药物（包括抗肿瘤坏死因子（TNF）生物制剂）反应不充分的类风湿性关节炎（RA）。RA的持续疗效可以通过利妥昔单抗的重复疗程来实现。然而，最佳剂量和利妥昔单抗在RA的再治疗方案仍有待建立。血清阳性、治疗后不久B细胞完全耗竭和既往使用不超过一种抗TNF药物失败是与利妥昔单抗更大临床获益相关的三个因素。约25%的RA患者发生首次利妥昔单抗给药后的输注反应，且发生率随后续暴露而降低。嵌合化合物的免疫原性发生在11%的RA患者中，但这与其在B细胞耗竭中的功效无关。RA随机对照试验的扩展观察并未显示与安慰剂组相比，与利妥昔单抗相关的严重感染发生率显著增加，感染率随时间保持不变。重复使用利妥昔单抗治疗与低丙种球蛋白血症相关，这可能会增加严重但很少机会性感染的风险。在接受利妥昔单抗治疗的RA患者中，有报告称隐性B型肝炎感染重新激活，但未观察到结核病发病率增加。筛查基线血清免疫球蛋白G水平和B型肝炎状态（包括隐匿性感染）非常重要，尤其是在B型肝炎感染流行的亚洲国家。必须注意与利妥昔单抗使用相关的罕见但致命的进行性多灶性白质脑病。上市后监测和登记数据，特别是在亚洲，是必要的，以建立长期的疗效和安全性利妥昔单抗治疗类风湿关节炎。
Rituximab is a chimeric monoclonal antibody that targets the CD20 molecule expressed on the surface of B cells. It was first used in the treatment of non-Hodgkin’s lymphoma and later approved for the treatment of rheumatoid arthritis (RA) that does not respond adequately to disease-modifying antirheumatic drugs, including the anti-tumor-necrosis-factor (TNF) biologics. Sustained efficacy in RA can be achieved by repeated courses of rituximab. However, the optimal dose and retreatment schedule of rituximab in RA remains to be established. Seropositivity, complete B cell depletion shortly after treatment, and previous failure to no more than one anti-TNF agent are three factors associated with greater clinical benefits to rituximab. Infusion reaction to the first dose of rituximab occurs in approximately 25% of RA patients, and the incidence reduces with subsequent exposure. Immunogenicity to the chimeric compound occurs in 11% of RA patients, but this does not correlate with its efficacy in B cell depletion. Extended observation of randomized controlled trials in RA does not reveal a significant increase in the incidence of serious infections related to rituximab compared to placebo groups, and the infection rate remains static over time. Repeated treatment with rituximab is associated with hypogammaglobulinemia, which may increase the risk of serious, but rarely opportunistic, infections. Reactivation of occult hepatitis B infection has been reported in RA patients receiving rituximab, but no increase in the incidence of tuberculosis was observed. Screening for baseline serum immunoglobulin G level and hepatitis B status (including occult infection) is important, especially in Asian countries where hepatitis B infection is prevalent. The rare but fatal progressive multifocal leukoencephalopathy linked to the use of rituximab has to be noted. Postmarketing surveillance and registry data, particularly in Asia, are necessary to establish the long-term efficacy and safety of rituximab in the treatment of RA.