Therapeutic Efficacy of Humanized Recombinant Anti-Interleukin-6 Receptor Antibody in Children With Systemic-Onset Juvenile Idiopathic Arthritis
Therapeutic Efficacy of Humanized Recombinant Anti-Interleukin-6 Receptor Antibody in Children With Systemic-Onset Juvenile Idiopathic Arthritis
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DOI：
10.1002/art.20944
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发表时间：
2005-03-01
影响因子：
--
通讯作者：
Kishimoto, Tadamitsu
中科院分区：
文献类型：
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作者：
Yokota, Shumpei;Miyamae, Takako;Kishimoto, Tadamitsu
客观的。目的 研究重组人抗白细胞介素 6 (抗 IL-6) 受体单克隆抗体 (MRA) 间接抑制 IL-6 对高剂量、长期皮质类固醇难治的全身性幼年特发性关节炎 (JIA) 儿童的安全性和有效性。方法。对 11 名符合纳入标准的活动性全身性幼年特发性关节炎儿童进行了个体剂量递增试验。所有患者首先静脉注射 2 mg/kg MRA。每个没有活动性炎症的儿童在两周后接受第二次相同的剂量，并在第二次剂量后两周接受第三次相同的剂量。根据实验室标记值出现疾病发作的儿童接受 4 毫克/公斤的剂量。在此剂量下没有疾病发作的患者在两周后接受第二次 4 mg/kg 剂量，并在第二次剂量后 2 周接受第三次 4 mg/kg 剂量，而患有活动性炎症的患者则额外接受 3 剂 8 mg/kg MRA。根据对 JIA 核心改进标准集的回复和实验室测试的结果，每两周评估一次功效。结果。根据发热发作、活动性关节炎、儿童健康评估问卷得分以及急性期反应物水平的评估结果，MRA 突然降低了 11 名儿童中 10 名的疾病活动度。然而，炎症反应物的水平会波动，直到每个孩子达到适当的 MRA 剂量。第三次固定剂量 MRA 两周后，90.9% 的所有患者有 30% 改善反应，90.9% 有 50% 改善反应，63.6% 有 70% 改善反应。结论。对患有活动性全身性疾病的儿童进行 MRA 治疗可导致临床改善和急性期反应物水平正常化。考虑到 IL-6 的不良影响和不良事件，MRA 安全且耐受性良好，并且比传统皮质类固醇提供更大的临床益处。
Objective. To investigate the safety and efficacy of a recombinant human anti-interieukin-6 (anti-IL-6) receptor monoclonal antibody (MRA) that indirectly inhibits the effects of IL-6 in children with systemic-onset juvenile idiopathic arthritis (JIA) refractory to high-dose, long-term corticosteroids.Methods. An individual escalating-dose trial was conducted in 11 children with active systemic-onset JIA who met the inclusion criteria. All were first administered an intravenous dose of 2 mg/kg MRA. Each child without active inflammation was given a second identical dose 2 weeks later and a third identical dose 2 weeks after the second dose. Children with disease flares according to laboratory marker values received a 4-mg/kg dose. Those without disease flares at this dose received a second 4-mg/kg dose 2 weeks later and a third 4-mg/kg dose 2 weeks after the second dose, while those with active inflammation received an additional 3 doses of 8 mg/kg MRA. Efficacy was evaluated every 2 weeks according to responses on the JIA core set of improvement criteria and the results of laboratory tests.Results. MRA abruptly reduced disease activity in 10 of the 11 children, as assessed by the occurrence of febrile episodes, active arthritis, scores on the Childhood Health Assessment Questionnaire, and levels of acute-phase reactants. However, levels of inflammatory reactants fluctuated until the proper MRA dose for each child was reached. Two weeks after the third fixed dose of MRA, 90.9% of all patients had a 30% improvement response, 90.9% had a 50% improvement response, and 63.6% had a 70% improvement response.Conclusion. MRA treatment of children with active systemic disease results in clinical improvement and in normalized levels of acute-phase reactants. MRA was safe and well tolerated and provided greater clinical benefit than conventional corticosteroids, considering the ill effects of IL-6 and adverse events.