Abstract: Objective　To explore the critical time points of tocilizumab in treating systemic-onset juvenile idiopathic arthritis （SJIA） and evaluate the short-term and long-term efficacy and safety of early use of tocilizumab. Methods　It is a multicenter prospective cohort study. We enrolled 88 children with first-onset moderate to severe active SJIA from 5 research centers，including Shenzhen Childrens Hospital，Childrens Hospital of Chongqing Medical University，Peking Union Medical College Hospital，Childrens Hospital of Fudan University，and Childrens Hospital of Nanjing Medical University，from November 1，2017，to November 1，2020. The patients were divided into tocilizumab group(n=51) and control group(n=37). After short-term （three months and six months） and long-term （one year and two years） treatment，we compared analyzed the clinical effects between the two groups. Results　The two groups C-reactive protein （CRP） and erythrocyte sedimentation rate （ESR） decreased significantly after 3 and 6 months of treatment，respectively. In the tocilizumab group，the two indices in more than 90% of patients decreased to the normal level，which had significant difference （P<0.05） compared with the control group. There were significant differences between the two groups in the dosage of hormone use at the initial stage（P<0.05），as well as after three and six months of treatment （P<0.05）. The hormone dosage was significantly reduced，and the proportion of the patients who successfully stopped using hormone in half a year increased significantly. The short-term compliance rates of ACRPedi 30/50/70/90 in tocilizumab group and control group were significantly different （P<0.05），being 100.0%/94.0%/70.0%/36.0% and 97.2%/77.8%/50.0%/8.3% after 3 months，and 100.0%/95.5%/84.4%/57.8% and 96.4%/64.3%/42.9%/10.7% after 6 months，respectively. Comparing the long-term efficacy between the two groups，the compliance rate of ACRPedi 70/90 in the tocilizumab group was significantly higher than that in the control group （P<0.05）. The most common adverse reaction was respiratory tract infections in the two groups，and no other serious adverse events occurred. Conclusion　The early use of tocilizumab in moderate and severe SJIA is effective. Tocilizumab can efficiently relieve the inflammatory index and reduce the hormone dosage，achieving the goal of rapidly reducing the dosage or even stopping the use of hormone. It provides a good effect on improving disease activity in the long time.

Key words: systemic-onset juvenile idiopathic arthritis, tocilizumab, multicenter clinical study

摘要： 目的　探讨托珠单抗治疗全身型幼年特发性关节炎（SJIA）的关键节点，评估早期使用托珠单抗的短期与长期的疗效和安全性。方法　采用多中心前瞻性队列研究方法，选择2017年11月1日至2020年11月1日在5个研究中心（深圳市儿童医院、重庆医科大学附属儿童医院、北京协和医院、复旦大学附属儿科医院、南京医科大学附属儿童医院）初发中重度活动期SJIA患儿88例，其中托珠单抗组（51例）和对照组（37例）。评估两组患儿治疗3个月、6个月、1年、2年临床疗效，并进行对比分析。结果　两组治疗3个月、6个月后C反应蛋白（CRP）、红细胞沉降率（ESR）均明显下降，且托珠单抗组CRP、ESR较治疗前降至正常的患儿比例超过90%，与对照组比较，差异有统计学意义（P＜0.05）；确诊后两组激素初始用量、治疗3个月、6个月后激素使用量比较，差异有统计学意义（P＜0.05），托珠单抗组激素使用量少，且半年内成功减停比例明显增多；托珠单抗组和对照组ACRPedi 30/50/70/90短期达标率分别为：治疗3个月100.0%/94.0%/70.0%/36.0%和97.2%/77.8%/50.0%/8.3%；治疗6个月100.0%/95.5%/84.4%/57.8%和96.4%/64.3%/42.9%/10.7%，两组比较差异有统计学意义（P＜0.05）；两组治疗12个月、24个月长期疗效比较，托珠单抗组ACRPedi 70 /90达标率明显高于对照组，差异有统计学意义（P＜0.05）。两组患儿的不良反应最常见为呼吸道感染，无严重不良事件发生。结论　托珠单抗早期用于治疗中重度SJIA疗效确切，托珠单抗能更快降低炎症指标，有效减少激素用量，实现激素快速减量，甚至停药，且对于长期改善疾病活动度疗效较佳。

关键词: 全身型幼年特发性关节炎, 托珠单抗, 多中心临床研究