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

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

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。

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.