Abatacept in the treatment of polyarticular JIA: development, clinical utility, and place in therapy.
Abatacept in the treatment of polyarticular JIA: development, clinical utility, and place in therapy.
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DOI：
10.2147/dddt.s16489
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发表时间：
2011-01-26
期刊：
影响因子：
--
通讯作者：
Hashkes PJ
中科院分区：
文献类型：
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作者：
Goldzweig O;Hashkes PJ
青少年特发性关节炎（JIA）是一组影响儿童的慢性关节炎。多发性关节炎类别，在前六个月内影响五个或更多关节，往往更具侵袭性，导致具有显著发病率，残疾和社会成本的破坏性关节疾病。目前的治疗方案主要是联合甲氨蝶呤和肿瘤坏死因子α (TNF-α)阻断，仍然有相当一部分患者反应不足。因此，开发通过其他发病机制起作用的新药物是必要的。T细胞淋巴细胞是JIA免疫反应的关键成分。细胞毒性淋巴细胞相关抗原-4 （CTLA-4）是激活T细胞所必需的共刺激途径的有效抑制剂。Abatacept是一种重组融合蛋白，包括人CTLA-4的细胞外部分与IgG-1修饰的Fc部分连接。在一项针对多关节性JIA儿童的随机、多国、盲法停药研究中，发现阿巴接受对约70%的患者有效，其中包括39%的TNF-α阻断失败，在停药阶段发生的急性发作明显少于接受安慰剂的患者。在一项为期三年的开放标签扩展研究中，Abatacept继续显示出良好的疗效，对健康相关的生活质量有有益的影响。abataccept的安全性总体上是好的。2008年，美国食品和药物管理局批准abataccept用于6岁以上JIA患儿和多关节疗程。2010年，欧洲药品管理局（European Medicines Agency）批准abataccept与甲氨蝶呤（methotrexate）联合使用，用于那些至少一种疾病改善药物和TNF-α阻断治疗失败的患者。
Juvenile idiopathic arthritis (JIA) is a group of chronic arthritides affecting children. The polyarthritis category, affecting five or more joints in the first six months, tends to be more aggressive, leading to a destructive joint disease with significant morbidity, disability, and costs to society. The current treatment regimen, which primarily combines methotrexate and tumor necrosis factor alpha (TNF-α) blockade, still leaves a significant group of patients with an inadequate response. Therefore, the development of new medications that act via other mechanisms of pathogenesis is necessary. T cell lymphocytes are key components in the immune reaction in JIA. Cytotoxic lymphocyte-associated antigen-4 (CTLA-4) is a potent inhibitor of the costimulation pathway necessary to activate T cells. Abatacept is a recombinant fusion protein comprising the extracellular part of human CTLA-4 connected to a modified Fc part of IgG-1. In a randomized, multinational, blinded withdrawal study in children with polyarticular JIA, abatacept was found to be effective in about 70% of the patients, including 39% of TNF-α blockade failures, with significantly fewer flares occurring during the withdrawal phase than in patients receiving placebo. Abatacept continued to show good efficacy in a three-year open-label extension study, with a beneficial effect on health-related quality of life. The safety profile of abatacept is generally good. In 2008, the US Food and Drug Administration approved abatacept for use in children over six years of age with JIA and a polyarticular course. In 2010, the European Medicines Agency gave approval for abatacept to be used in combination with methotrexate for those who fail at least one disease-modifying medication and TNF-α blockade.