托珠单抗在儿童风湿免疫性疾病中应用的安全性研究

Safety of tocilizumab in children with rheumatic immune disease

目的分析托珠单抗在儿童风湿免疫性疾病中应用的安全性,为临床用药提供参考。方法收集2016年1月1日—2022年8月9日使用托珠单抗治疗风湿免疫性疾病患儿的临床资料,对不良事件(AE)的发生率及影响因素、分布、发生时间和转归等进行回顾性分析。结果共纳入53例使用托珠单抗治疗的患儿,全身型幼年特发性关节炎48例、干燥综合征1例、自身免疫疾病(自身炎症性疾病)2例、幼年特发性关节炎(多关节型)1例。多发性大动脉炎1例,AE发生率为87%(46/53),主要AE为高甘油三酯血症(60%)、肝损伤(49%)、高胆固醇血症(30%)、高胆红素血症(8%)、中性粒细胞减少(9%)、超敏反应(8%)等。导致停药的主要AE为超敏反应,高胆固醇血症的发生与更高的给药剂量相关,肝损伤的发生与更高年龄和更高体重指数相关。AE大部分较轻,可自行恢复正常,持续用药率96%(44/46)。结论儿童使用托珠单抗治疗后相关AE发生率较高,超敏反应可导致停药,用药期间需要予以关注。虽然大部分患儿只发生轻度肝损伤,仍需警惕严重肝衰竭的发生可能。

AIM To analyze the safety of tocilizumab in children with rheumatic immune disease and provide reference for clinical medication.METHODS The medical records of tocilizumab from January 1st,2016 to August 9th,2022 through the medical record system were collected.Retrospective analysis of the adverse events(AE)incidence and influencing factors,distribution,occurrence time,and outcome.RESULTS A total of 53 children treated with tocilizumab were included,48 cases of systemic juvenile idiopathic arthritis,1 case of Sjogren's syndrome,2 cases of autoimmune disease(autoimmune disease),1 case of juvenile idiopathic arthritis(polyarticular type),and 1 case of multiple arteritis.The incidence of AE was 87%(46/53).The main AE were hypertriglyceridemia(60%),liver injury(49%),hypercholesterolemia(30%),hyperbilirubinemia(8%),neutropenia(9%),hypersensitivity(8%).Hypersensitivity was the main AE leading to drug withdrawal.The occurrence of hypercholesterolemia was associated with higher dose,and the occurrence of liver injury was associated with higher age and higher body mass index.Most of AE were mild and could recover to normal without treatment,and continuous medication rate was 96%(44/46).CONCLUSION The incidence of AE related to the use of tocilizumab in children is high.Hypersensitivity reactions may lead to drug withdrawal,and attention should be paid during the medication period.Although most children only suffer from mild liver injury,it is still necessary to be alert to the possibility of severe liver failure.