Scott D L
Department of Rheumatology, GKT School of Medicine, Weston Education Centre, Kings College, London, UK.
Int J Clin Pract. 2005 Jan;59(1):114-8. doi: 10.1111/j.1742-1241.2005.00380.x.
Tumour necrosis factor-alpha (TNF-alpha) is one of the inflammatory cytokines. It is released by activated monocytes, macrophages and T lymphocytes and promotes inflammation. TNF-alpha binds to two receptors; one of these is the type 2 TNF receptor (p75). Etanercept is a soluble TNF-receptor fusion protein. It consists of two linked dimmers, each with a ligand-binding portion of the higher affinity type 2 TNF receptor (p75). This fusion protein binds to TNF-alpha and prevents it from interacting with its receptor. Etanercept is given by subcutaneous administration at a dose of 25 mg twice a week. This dosing reflects its half-life of about 4 days. Clinical trials show etanercept is effective and safe to use in rheumatoid arthritis (RA). It reduces disease activity and limits progressive joint damage in both early and late disease. It can be used as a monotherapy or in combination with methotrexate, and in this, the latter approach appears most effective. It is also effective in psoriatic arthritis and ankylosing spondylitis. Although the biologic appears safe, caution is needed to ensure it does not re-activate tuberculosis. It should not be used in patients with disseminated sclerosis, and there are concerns about a potential relationship to lymphoma. Its high cost means there will be continuing debate about the ideal position of this new biologic within the treatment pathway of RA. At present, it is recommended for use when methotrexate and another disease-modifying drug have failed.
肿瘤坏死因子-α(TNF-α)是炎症细胞因子之一。它由活化的单核细胞、巨噬细胞和T淋巴细胞释放,促进炎症反应。TNF-α与两种受体结合;其中之一是2型TNF受体(p75)。依那西普是一种可溶性TNF受体融合蛋白。它由两个相连的二聚体组成,每个二聚体都有高亲和力2型TNF受体(p75)的配体结合部分。这种融合蛋白与TNF-α结合,阻止其与受体相互作用。依那西普通过皮下给药,剂量为25mg,每周两次。这种给药方式反映了其约4天的半衰期。临床试验表明,依那西普在类风湿关节炎(RA)的治疗中有效且安全。它能降低疾病活动度,限制早期和晚期疾病中关节的进行性损伤。它可以作为单一疗法使用,也可以与甲氨蝶呤联合使用,其中后一种方法似乎最有效。它在银屑病关节炎和强直性脊柱炎中也有效。尽管这种生物制剂看起来安全,但仍需谨慎使用以确保不会重新激活结核病。它不应在患有播散性硬化症的患者中使用,并且人们担心它与淋巴瘤之间可能存在的关系。其高昂的成本意味着对于这种新型生物制剂在RA治疗途径中的理想地位将持续存在争议。目前,推荐在甲氨蝶呤和另一种改善病情的药物治疗失败时使用。