Current perspectives on tocilizumab for the treatment of rheumatoid arthritis: a review.
Current perspectives on tocilizumab for the treatment of rheumatoid arthritis: a review.
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DOI：
10.2147/ppa.s41433
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发表时间：
2013
影响因子：
2.2
通讯作者：
Scott DL
中科院分区：
文献类型：
--
作者：
Al-Shakarchi I;Gullick NJ;Scott DL
类风湿关节炎(RA)仍然是一个主要的临床问题，许多患者持续的全身炎性疾病导致进行性侵蚀性损害和高水平的残疾。一系列促炎细胞因子包括肿瘤坏死因子、白介素1和白介素6参与了类风湿关节炎的发病过程，这些细胞因子可以被生物制剂特异性地抑制。托西珠单抗(tocilizumab，TCZ)是一种重组人源化抗IL-6受体单抗，每月静脉滴注可阻断IL-6信号转导。有强有力的证据表明，它在临床上是有效的，而且具有成本效益。已经有几个关键的临床试验评估了TCZ在RA患者中的安全性和有效性。我们回顾了5个II期试验和7个III期试验，分别招募了626名和5268名RA患者。在所有试验中，美国风湿病学会(ACR)的反应标准被用作主要或次要结果衡量标准。总体而言，这些试验表明，TCZ在许多患者组中治疗RA是有效的，包括那些对甲氨蝶呤(MTX)或肿瘤坏死因子抑制反应不足的患者。曲克西平作为单一疗法和与甲氨蝶呤联合使用，在开始治疗的几周内改善了类风湿性关节炎的体征和症状。此外，TCZ被证明可以减少放射学疾病的进展，改善身体功能，无论是作为单一疗法还是与MTX联合使用。一项为期5年的扩展研究表明，TCZ保持了良好的长期疗效和安全性。TCZ总体耐受性良好。尽管它的使用增加了不良事件的风险，但与对照组相比，这些不良事件的严重程度通常是轻度到中度的，治疗不会增加严重不良事件的风险。由于服用TCZ的患者血清总胆固醇、甘油三酯、高密度脂蛋白和血清转氨酶水平适度上升，以及一些患者出现严重的中性粒细胞减少，建议定期监测全血细胞计数、肝功能和血脂。鉴于其在治疗RA方面的临床疗效，TCZ可能有益于其他自身免疫性疾病的治疗，在这些疾病中，IL-6在炎症级联反应中发挥作用。
Rheumatoid arthritis (RA) remains a major clinical problem with many patients having continuing systemic inflammatory disease resulting in progressive erosive damage and high levels of disability. A range of pro-inflammatory cytokines including tumor necrosis factor (TNF), interleukin (IL)-1 and IL-6 are involved in RA pathogenesis; these cytokines can be specifically inhibited by biological agents. Tocilizumab (TCZ) is a recombinant humanized anti-IL-6 receptor monoclonal antibody, administered monthly by intravenous infusion that prevents IL-6 signal transduction. There is strong evidence that it is both clinically efficacious and cost-effective. There have been several key clinical trials evaluating the safety and efficacy of TCZ in RA patients. We review five Phase II trials and seven Phase III trials enrolling a total of 626 and 5268 RA patients respectively. The American College of Rheumatology (ACR) response criteria were used as the primary or secondary outcome measure in all trials. Overall these trials demonstrated that TCZ was effective in the treatment of RA in a number of patient groups, including those with an inadequate response to methotrexate (MTX) or TNF inhibition. TCZ use, both as monotherapy and in combination with MTX, improved the signs and symptoms of RA within several weeks of commencing treatment. Additionally, TCZ was shown to reduce radiological disease progression and improve physical function, both as monotherapy and in combination with MTX. A 5-year extension study demonstrated that TCZ sustained good long-term efficacy and safety profiles. TCZ was generally well tolerated. Although its use increased the risk of an adverse event, these were usually mild to moderate in severity and treatment did not increase the risk of a serious adverse event in comparison to controls. Due to moderate increases in serum levels of total cholesterol, triglycerides, high-density lipoproteins and serum transaminases seen in those patients treated with TCZ, as well as severe neutropenia in some, regular blood monitoring of full blood count, liver function and lipids is recommended. Given its clinical efficacy in the treatment of RA, TCZ may be beneficial in the treatment of other autoimmune diseases where IL-6 plays a role in the inflammatory cascade.