托珠单抗与依那西普治疗多关节炎型幼年特发性关节炎临床研究

Clinical observation of tocilizumab and etanercept for polyarticular course juvenile idiopathic arthritis

目的:探讨托珠单抗与依那西普治疗多关节炎型幼年特发性关节炎(polyarticular juvenile idiopathic arthritis,pJIA)患儿的临床疗效,免疫调节作用及安全性差异。方法:选择2017年1月至2019年3月在浙江大学医学院附属儿童医院诊治的24例重度活动性pJIA患儿,分为托珠单抗组12例和依那西普组12例,分别记录两组患儿治疗前、治疗3个月、6个月、12个月时的临床症状、实验室指标及不良反应情况,并进行对比分析。结果:治疗3个月时,托珠单抗组和依那西普组的关节肿胀数、关节压痛或活动时疼痛数、C反应蛋白(CRP)、红细胞沉降率(ESR)及JADAS 27评分均较治疗前有明显改善(P<0.05);且托珠单抗组的CRP、ESR、JADAS 27评分比依那西普组下降更明显(P<0.05)。治疗6个月时,托珠单抗组CD19^+B、CD4^+T细胞比例、IgG、IgA、IgM、C3、C4下降和CD8^+T细胞比例升高,比较治疗前差异有统计学意义;依那西普组IgG和IgA较治疗前明显下降;托珠单抗组IgG、IgA、IgM、C3、C4比依那西普组下降更明显(P<0.05)。治疗12个月时,托珠单抗组和依那西普组的JADAS 27低疾病活动度率分别为36.4%和37.5%;两组的ACR Pedi 30/50/70/90分别达到100%/100%/87.5%/62.5%和100%/100%/81.9%/45.5%的缓解。两组患儿的不良反应最常见为感染,无严重不良事件发生。结论:托珠单抗与依那西普治疗pJIA疗效确切,托珠单抗能更快降低炎症指标,改善疾病活动度,并可调节亢进的体液免疫及调节CD4^+T、CD19^+B细胞。

AIM:To observe and evaluate the clinical effect,immunomodulatory and safety of the tocilizumab and etanercept for patients with polyarticular juvenile idiopathic arthritis(pJIA).METHODS:Twenty-four pJIA patients of high disease activity were admitted from January 2017 to March 2019.All patients were divided into the tocilizumab group(12 cases)and the etanercept group(12 cases).Improvements of clinical symptoms,laboratory parameters and adverse reactions were evaluated and compared between these two groups at pretherapy and 3,6,12 months after the primary treatment.RESULTS:Compared with before treatment,the number of joint swelling,joint tenderness or pain during movement,C-reactive protein(CRP),erythrocyte sedimentation rate(ESR)and JADAS 27 scores in the tocilizumab group and the etanercept group were significantly improved(P<0.05)at 3 months after treatment.Moreover,CRP,ESR and JADAS 27 scores of the tocilizumab group decreased more significantly than those of the etanercept group(P<0.05).Compared with before treatment,the proportion of CD19^+B and CD4^+T cells,the decrease of IgG,IgA,IgM,C3,C4 and the proportion of CD8^+T cells in the tocilizumab group were statistically significantat 6 months after treatment;IgG and IgA in the etanercept group were significantly lower than before treatment;IgG,IgA,IgM,C3,and C4 in the tocilizumab group were significantly lower than those of the etanercept group(P<0.05).At 12 months of treatment,the low disease activity rates of JADAS 27 in the tocilizumab group and the etanercept group were 36.4%and 37.5%,respectively;the ACR Pedi 30/50/70/90 in the two groups reached 100%/100%/87.5%/62.5%and 100%/100%/81.9%/45.5%relief.The most common adverse reaction was infection;meanwhile no significant adverse event happened.CONCLUSION:Tocilizumab and etanercept are effective for pJIA.Tocilizumab can quickly reduce the inflammatory parameters,improve disease activity,and regulate CD4^+T,CD19^+B cells.