Department of Pediatrics, Yokohama City University School of Medicine, Kanazawa-ku, Yokohama, Kanagawa, Japan.
Expert Rev Clin Immunol. 2010 Sep;6(5):735-43. doi: 10.1586/eci.10.41.
Systemic juvenile idiopathic arthritis (JIA) is a subtype of chronic childhood arthritis of unknown etiology, manifested by long-lasting systemic inflammation and complicated by joint destruction, functional disability and growth impairment. Macrophage activation syndrome is the most devastating complication, which is associated with serious morbidity. IL-6 has been hypothesized to be a pathogenic factor of this disease. The anti-IL-6 receptor monoclonal antibody, tocilizumab, was developed, and we investigated the safety and efficacy of tocilizumab in children with this disorder. The Phase II trial revealed that high-grade fever abruptly subsided and that inflammatory markers were also normalized. The dose of tocilizumab for systemic JIA was revealed to be 8 mg/kg at 2-week intervals. The Phase III trial, a placebo-controlled, double-blind study, indicated that patients in the tocilizumab group had sustained clinical measures of effectiveness and wellbeing, whereas most of those in the placebo group needed rescue treatment. The most common adverse events were symptoms of mild infections and transient increases of alanine aminotransferase. Serious adverse events were anaphylactoid reaction and gastrointestinal hemorrhage. Clinical and laboratory improvement in fever, sickness behavior, C-reactive protein gene expression and chronic inflammatory anemia in children with systemic JIA treated with tocilizumab indicated the possible roles played by IL-6 in this inflammatory disease. Thus, tocilizumab is generally safe and well tolerated. It might be a suitable treatment in the control of this disorder, which has so far been difficult to manage.
全身性幼年特发性关节炎（JIA）是一种病因不明的慢性儿童关节炎，表现为持久的全身炎症，并伴有关节破坏、功能障碍和生长受损。巨噬细胞活化综合征是最具破坏性的并发症，与严重发病率相关。IL-6 被假设为这种疾病的致病因素。抗 IL-6 受体单克隆抗体，托珠单抗被开发出来，并对其在患有这种疾病的儿童中的安全性和疗效进行了研究。II 期试验表明，高热突然消退，炎症标志物也恢复正常。全身性 JIA 的托珠单抗剂量为 8mg/kg，每 2 周一次。III 期安慰剂对照、双盲研究表明，托珠单抗组患者的临床疗效和生活质量持续得到改善，而安慰剂组大多数患者需要进行抢救治疗。最常见的不良反应是轻度感染症状和丙氨酸氨基转移酶短暂升高。严重不良反应为类过敏反应和胃肠道出血。全身性 JIA 儿童接受托珠单抗治疗后，发热、疾病行为、C 反应蛋白基因表达和慢性炎症性贫血的临床和实验室改善表明，IL-6 在这种炎症性疾病中可能发挥作用。因此，托珠单抗通常是安全且耐受良好的。对于这种迄今为止难以控制的疾病，它可能是一种合适的治疗选择。
