Department of Pediatrics, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan.
Mod Rheumatol. 2010 Apr;20(2):107-13. doi: 10.1007/s10165-009-0259-9. Epub 2010 Jan 20.
Etanercept is a dimeric fusion protein consisting of the extracellular domain of human tumor necrosis factor receptor II (TNFR II, molecular weight 75 kDa) coupled to the Fc region of human immunoglobulin (IgG1). It is produced by recombinant DNA technology by first introducing the gene into Chinese hamster ovarian cells and then purifying the protein from the culture supernatant. The mechanism of action of etanercept consists of binding to serum TNF-alpha and lymphotoxin (LT)-alpha (TNF-beta), which prevents TNF-alpha and LT-alpha from binding to the TNF-alpha receptor on the plasma membrane of the target cell. Etanercept is currently approved for treating adult rheumatoid arthritis (RA) in more than 70 countries worldwide. In Japan, it was approved for this target group in January 2005. The USA and Europe were the first to approve entanercept for use in treating juvenile idiopathic arthritis (JIA), initially for the treatment of active polyarticular JIA in patients not responding to disease-modifying antirheumatic drugs (USA in May 1999, followed by the EU in February 2000). Thereafter, the drug received approval for the treatment of JIA in many other countries. In Japan, children who have been diagnosed and treated according to Yokota et al. (Mod Rheumatol 17:353-363, 2007), but who have responded poorly to treatment must move onto the next stage of treatment. Such treatments include biological drugs, which, however, should be used with strict adhesion to the indications and exclusion criteria and should be used, for the time being, only by physicians trained on how to use them. In Japan, etanercept was approved in July 2009 for use in children. Although this drug has brought about a revolutionary advance in the treatment of JIA, it is our task to maximize its therapeutic effects and minimize its toxic effects. The guidelines presented here define the indications, exclusion criteria, usage, and evaluation criteria of etanercept for the treatment of polyarticular JIA.
依那西普是一种二聚体融合蛋白，由人肿瘤坏死因子受体Ⅱ（TNFRⅡ，分子量 75 kDa）的细胞外结构域与人类免疫球蛋白（IgG1）的 Fc 区连接而成。它通过重组 DNA 技术生产，首先将基因导入中国仓鼠卵巢细胞，然后从培养上清液中纯化该蛋白。依那西普的作用机制包括与血清 TNF-α和淋巴毒素（LT）-α（TNF-β）结合，从而阻止 TNF-α和 LT-α与靶细胞膜上的 TNF-α受体结合。依那西普目前已在全球 70 多个国家批准用于治疗成人类风湿关节炎（RA）。在日本，它于 2005 年 1 月被批准用于该目标人群。美国和欧洲是最早批准依那西普用于治疗青少年特发性关节炎（JIA）的国家，最初用于治疗对疾病修饰抗风湿药物无反应的多关节 JIA 患者（美国于 1999 年 5 月，欧盟于 2000 年 2 月）。此后，该药物在许多其他国家获得批准用于治疗 JIA。在日本，根据 Yokota 等人（Mod Rheumatol 17:353-363, 2007）诊断和治疗的儿童，如果治疗反应不佳，必须进入下一阶段的治疗。这些治疗方法包括生物药物，但应严格遵守适应证和排除标准，并且暂时只能由接受过如何使用这些药物培训的医生使用。在日本，依那西普于 2009 年 7 月被批准用于儿童。虽然该药物在治疗 JIA 方面带来了革命性的进步，但我们的任务是最大限度地发挥其治疗效果，最大限度地减少其毒副作用。本指南定义了依那西普治疗多关节 JIA 的适应证、排除标准、用法和评估标准。
