中国实用儿科杂志

中国实用儿科杂志 ›› 2021, Vol. 36 ›› Issue (11): 858-868.DOI: 10.19538/j.ek2021110612

• 论著 • 上一篇    下一篇

贝利尤单抗治疗中国儿童系统性红斑狼疮28周有效性和安全性分析：一项回顾性多中心真实世界的初步研究

  

  1. 执　笔：曾　萍 专家组：黄文彦，俞海国，卢美萍，郑雯洁，檀卫平，王亚军，周建华，党西强，张秋业，唐雪梅，曾华松  参与单位及成员（排名不分先后）：广州市妇女儿童医疗中心（曾　萍，曾华松）；中南大学湘雅二医院（李永珍，党西强）；重庆医科大学附属儿童医院（唐文静，唐雪梅）；青岛大学附属医院（王大海，张秋业）；华中科技大学同济医学院附属同济医院（张　瑜，周建华）；云南省第一人民医院（曹志琅，王亚军）；中山大学孙逸仙纪念医院（张碧红，檀卫平）；温州医科大学附属育英儿童医院（董翌玮，郑雯洁）；浙江大学医学院附属儿童医院（郑　琪，卢美萍）；南京医科大学附属儿童医院（马　乐，俞海国）；上海交通大学附属儿童医院（钮小玲，黄文彦）；海南省妇女儿童医学中心（徐志泉）；江西省儿童医院（刘小惠）；安徽省儿童医院（陈雨青）；中山大学附属第五医院（廖　娟，张　桦）；佛山市第一 人民医院（何逾祥）；广州市第一人民医院华南理工大学附属第二医院（郝志宏）；苏州大学附属儿童医院（唐韩云，李晓忠）；上海交通大学医学院附属上海儿童医学中心（张晨星）；贵阳市妇幼保健院（蒋新辉，邵晓珊）；暨南大学附属第一医院（杨　方）；西安交通大学附属儿童医院（李小青）；山东大学附属省立医院（王　莉，孙书珍）；中国医科大学 附属盛京医院（朱万红）；江门市中心医院（冯明亮）；昆明医科大学附属儿童医院（赵　波）；广东省第二人民医院（郑少玲）；广西医科大学第一附属医院（杨昌融）；中山大学附属第一医院（裴瑜馨，蒋小云）；河北医科大学附属河北省 儿童医院（张东风）；南方医科大学珠江医院（陈剑锋）；河北医科大学第二医院（戎赞华）；四川大学华西第二医院（郭妍南）；华中科技大学同济医学院附属武汉儿童医院（刘　凡，尹　薇）；电子科技大学医学院附属妇女儿童医院·成都市妇女儿童中心医院（张　伟）；乌鲁木齐儿童医院（赵冬梅）；武汉大学人民医院（李　弢）
  • 出版日期:2021-11-06 发布日期:2022-01-04
  • 通讯作者: 曾华松，电子信箱：huasongxuqing@163.com；唐雪梅，电子信箱：tangxuemei2008@163.com；张秋业，电子信箱：qyzh9816@163.com；党西强，电子信箱：tongxunzzdxq@163.com

Efficacy and safety analysis of belimumab for 28 weeks in real-world Chinese children with systemic lupus erythematosus：A retrospective multicenter pilot study

  • Online:2021-11-06 Published:2022-01-04

摘要： 目的　评价贝利尤单抗在中国儿童系统性红斑狼疮（systemic lupus erythematosus，SLE）中应用28周的疗效和安全性。方法　回顾性分析2019年9月至2021年2月在国内37家三甲医院的371例系统性红斑狼疮患儿临床资料，选取169例使用贝利尤单抗的系统性红斑狼疮患儿作为贝利尤治疗组研究对象，87例基线SLEDAI评分相似的、同期应用传统免疫抑制药物治疗的患儿作为传统药物治疗组，进行为期28周的治疗；采用1997年美国风湿病学会修订的SLE诊断标准、儿童SLE疾病活动评估工具SLEDAI-2K评估患儿用药后的有效性、安全性及使用状况。结果　纳入贝利尤治疗组的169例患儿平均病程为25.00±27.97个月，完成治疗28周后，贝利尤治疗组和传统药物治疗组患儿SLEDAI评分、ANA和dsDNA阳性率均明显下降，差异无统计学意义；在观察终点（28周），两组方案治疗后口服激素的量都减少，贝利尤治疗组减少更明显（P<0.05）；贝利尤治疗组28周治疗后仍有50%的患儿存在不同程度的肾脏损伤，但与治疗前相比有明显的好转（69.2%vs.50.0%，P<0.05），传统药物治疗组患儿的肾脏损伤较治疗前无明显好转（56.3%vs.43.4%，P>0.05）；贝利尤治疗组监测终点28周达到LLDAS以上患儿的比例达到40.5%，其中9%的患儿临床缓解，而传统药物治疗组28周达到LLDAS以上患儿的比例仅8.8%，其中3.5%的患儿临床缓解，达标治疗比例低于贝利尤治疗组（Logistic回归分析，P<0.001）；与传统药物治疗相比，贝利尤治疗组发生感染的次数较少。结论　贝利尤单抗治疗儿童系统性红斑狼疮，能够减少激素和传统免疫抑制药物的用量；更容易达到LLDAS和临床缓解状态，有利于达标治疗；贝利尤单抗治疗对儿童狼疮性肾炎较传统药物治疗有优势；贝利尤单抗治疗发生感染等不良事件的发生率低。

关键词: 儿童, 系统性红斑狼疮, 贝利尤单抗, 有效性, 安全性

Abstract: Objective　To evaluate the efficacy and safety of 28-week use of belimumab in Chinese children with systemic lupus erythematosus（SLE）. Methods　The study was undertaken by a questionnaire completed in 37 Grade 3A hospitals’ Rheumatology and immunology department in China. To evaluate the efficacy，safety and use of Belimumab in the diagnosis of systemic Lupus Erythematosus of children with the age of 5-18 years during September，2019 to February， 2021. At the same time，patients with SLE who had similar baseline of SLEDAI score and were treated with traditional immunosuppressive drug at the same hospital were selected as a control cohort. Result　The average course of disease was 25.00±27.97 months in 169 children who were treated with belimumab. After 28 weeks of treatment，SLEDAI score，ANA and dsDNA positive rates were significantly decreased in the belimumab-treated group and the traditional treatment group，the difference being with no statistical significance. At the observation end point（28w），the amount of oral hormone was significantly decreased in both groups after treatment（P<0.05）；after 28 weeks of treatment，50% of the children in the belimumab group still had kidney injury of varying degrees，but significantly improved compared with before treatment（69.2% vs. 50%，P<0.05），while the children in the conventional treatment group had no significant improvement compared with before treatment（56.3% vs. 43.4%，P>0.05）. The proportion of patients at the endpoint of 28w reaching the status of LLDAS or remission in the belimumab group was 40.5%，of whom 9% were in clinical remission，while the proportion of patients in the conventional group was only 8.8% whe reached the status of LLDAS，of whom 3.5% were in clinical remission，and the proportion of qualified treatment was lower than that of the belimumab treatment group（Logistic regression analysis，P<0.001）. A lower number of infections occurred in the belimumab group than in the conventional treatment group. Conclusion　Targeted therapy of systemic lupus erythematosus in children with belimumab can reduce the dosage of hormone and traditional immunosuppressive drug. It is more likely to achieve LLDAS and clinical remission and belimumab could be the biologic DMARDs. The incidence of adverse events，such as infections，is low with the use of belimumab，and its effects on lupus nephritis are better than conventional drugs.

Key words: child, systemic lupus erythematosus, belimumab, effectiveness, safety