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新型生物制剂和细胞因子拮抗剂在幼年特发性关节炎(JIA)治疗中的重要性

[Importance of the new biologicals and cytokine antagonists in the treatment of juvenile idiopathic arthritis (JIA)].

作者信息

Horneff G

机构信息

Asklepios Klinik für Kinder- und Jugendmedizin Sankt-Augustin, 53757 Sankt Augustin.

出版信息

Z Rheumatol. 2005 Jun;64(5):317-26. doi: 10.1007/s00393-005-0748-y.

DOI:10.1007/s00393-005-0748-y
PMID:15965816
Abstract

Juvenile idiopathic arthritis is group of diseases of unknown aetiology characterised by the occurrence of chronic arthritis during childhood. Compared to adult onset rheumatoid arthritis, its course is more variable. Increasing knowledge of the inflammatory process as well as in molecular genetics and biotechnology has enable the production of new drugs, the biologicals. These are able to specifically block mechanisms of immune activation and thereby interfere with the inflammatory process. An increasing number of biologicals have been tried in clinical studies in adults suffering from rheumatoid arthritis, psoriasis or psoriasis arthritis and a couple of them were already licensed for treatment. Treatment of juvenile idiopathic arthritis by blockade of tumournecrosis-factor (TNF) using the soluble receptor Etanercept or the monoclonal antibodies Infliximab and Adalimumab showed comparable clinical efficacy. Blockade of TNF therefore already reached a certain place in the therapeutic algorythm for treatment of juvenile idiopathic arthritis. Currently, only Etanercept is licensed for treatment of active juvenile polyarthritis refractory to methotrexate. Studies using Infliximab and Adalimumab will be completed in the near future. However, antibodies blocking TNF may already be used in patients suffering from active uncontrolled chronic uveitis in whom visual impairment is threatening. TNF blockers may also be indicated in juvenile ankylosing spondylitis. The use of further biologicals, the interleukin-1 receptor antagonist Anakinra, Atlizumab (MRA) blocking the receptor for interleukin-6 or Abatacept, an inhibitory ligand of the co-stimulatory T cell membrane molecule CD28, remain experimental and should be preserved for clinical studies.

摘要

青少年特发性关节炎是一组病因不明的疾病,其特征是在儿童期出现慢性关节炎。与成人发病的类风湿关节炎相比,其病程更具变异性。随着对炎症过程以及分子遗传学和生物技术认识的不断增加,已经能够生产新的药物,即生物制剂。这些药物能够特异性地阻断免疫激活机制,从而干扰炎症过程。越来越多的生物制剂已在患有类风湿关节炎、银屑病或银屑病关节炎的成人临床研究中进行试验,其中一些已获批准用于治疗。使用可溶性受体依那西普或单克隆抗体英夫利昔单抗和阿达木单抗阻断肿瘤坏死因子(TNF)治疗青少年特发性关节炎显示出相当的临床疗效。因此,TNF阻断在青少年特发性关节炎的治疗算法中已占据一定地位。目前,只有依那西普被批准用于治疗对甲氨蝶呤难治的活动性青少年多关节炎。使用英夫利昔单抗和阿达木单抗的研究将在不久后完成。然而,阻断TNF的抗体可能已用于患有活动性未控制的慢性葡萄膜炎且视力受到威胁的患者。TNF阻滞剂也可能适用于青少年强直性脊柱炎。使用其他生物制剂,如白细胞介素-1受体拮抗剂阿那白滞素、阻断白细胞介素-6受体的阿特珠单抗(MRA)或共刺激T细胞膜分子CD28的抑制性配体阿巴西普,仍处于试验阶段,应保留用于临床研究。

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本文引用的文献

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Therapeutic efficacy of humanized recombinant anti-interleukin-6 receptor antibody in children with systemic-onset juvenile idiopathic arthritis.人源化重组抗白细胞介素-6受体抗体治疗全身型幼年特发性关节炎患儿的疗效
Arthritis Rheum. 2005 Mar;52(3):818-25. doi: 10.1002/art.20944.
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A randomized, placebo-controlled, double-masked clinical trial of etanercept for the treatment of uveitis associated with juvenile idiopathic arthritis.一项关于依那西普治疗青少年特发性关节炎相关葡萄膜炎的随机、安慰剂对照、双盲临床试验。
Arthritis Rheum. 2005 Feb 15;53(1):18-23. doi: 10.1002/art.20904.
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Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis.
利妥昔单抗靶向B细胞治疗对类风湿关节炎患者的疗效。
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Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial.在接受甲氨蝶呤联合治疗的活动性类风湿关节炎患者中,使用阿达木单抗(一种人抗肿瘤坏死因子单克隆抗体)治疗的影像学、临床及功能转归:一项随机、安慰剂对照、为期52周的试验。
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Delayed maculopapular, urticarial rash due to infliximab in two children with systemic onset juvenile idiopathic arthritis.两名系统性发作幼年特发性关节炎患儿因英夫利昔单抗出现延迟性斑丘疹、荨麻疹样皮疹。
Rheumatology (Oxford). 2004 May;43(5):674-5. doi: 10.1093/rheumatology/keh142.
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Tuberculosis in a nine-year-old girl treated with infliximab for systemic juvenile idiopathic arthritis.一名九岁女童因系统性幼年特发性关节炎接受英夫利昔单抗治疗后发生的结核病。
Rheumatology (Oxford). 2004 Apr;43(4):527-9. doi: 10.1093/rheumatology/keh074.
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Successful short term treatment of patients with severe undifferentiated spondyloarthritis with the anti-tumor necrosis factor-alpha fusion receptor protein etanercept.使用抗肿瘤坏死因子-α融合受体蛋白依那西普成功短期治疗重度未分化脊柱关节炎患者。
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