重组人Ⅱ型肿瘤坏死因子受体–抗体融合蛋白治疗非全身型幼年特发性关节炎的临床研究

Clinical study on Recombinant Human Tumor Necrosis Factor-α ReceptorⅡ: Ig G Fc Fusion Protein for injection in treatment of non systemic juvenile idiopathic arthritis

目的：探讨重组人Ⅱ型肿瘤坏死因子受体–抗体融合蛋白治疗非全身型幼年特发性关节炎的临床疗效。方法选择2010年9月-2013年9月湖北医药学院附属东风医院收治的非全身型幼年特发性关节炎患儿100例，随机分为对照组和治疗组，每组各50例。对照组给予常规药物治疗。治疗组在对照组基础上皮下注射注射用重组人Ⅱ型肿瘤坏死因子受体–抗体融合蛋白，0.4 mg/kg，2次/周。治疗3个月后根据患儿病情进行剂量调整，若患儿效果较好，则重组人Ⅱ型肿瘤坏死因子受体–抗体融合蛋白改为1次/周。两组均连续治疗6个月。观察两组的临床疗效，同时比较两组治疗前后肿瘤坏死因子α（TNF-α）、C反应蛋白（CRP）、白细胞介素-1β（IL-1β）、基质金属蛋白酶-3（MMP-3）、β胶原分解片断（β-CTx）、碱性磷酸酶（ALP）、白细胞计数（WBC）、血沉（ESR）和血小板计数（PLT）的变化。监测两组前臂、L2-4腰椎正侧位和股骨Ward’s三角骨密度的变化情况。结果治疗后，对照组和治疗组的总有效率分别为68.0%、88.0%，两组比较差异有统计学意义（P＜0.05）。治疗后，两组患儿TNF-α、CRP、IL-1β、MMP-3、WBC、ESR、PLT水平均显著下降，ALP显著升高，同组治疗前后差异有统计学意义（P＜0.05）；且治疗组的改善程度优于对照组，两组比较差异有统计学意义（P＜0.05）。治疗后，两组患儿腰椎正位、腰椎侧位骨密度显著上升，与治疗前相比差异有统计学意义（P＜0.05）；且治疗组治疗后腰椎正位、腰椎侧位骨密度显著高于对照组，两组比较差异有统计学意（P＜0.05）。结论重组人Ⅱ型肿瘤坏死因子受体–抗体融合蛋白治疗非全身型幼年特发性关节炎具有较好的临床疗效，可改善患儿骨质疏松状况，其作用机制可能与降低患儿血清炎症因子水平有关。

ObjectiveTo investigate the clinical effect of Recombinant Human Tumor Necrosis Factor-α ReceptorⅡ： IgG Fc Fusion Protein for injection in treatment of non systemic juvenile idiopathic arthritis.Methods Patients （100 cases） with non systemic juvenile idiopathic arthritis in Dongfeng Hospital, Hubei University of Medicine from September 2010 to September 2013 were randomly divided into control and treatment groups, and each group had 50 cases. The patients in the control group were given routine drug. The patients in the treatment group weresc administered with Recombinant Human Tumor Necrosis Factor-α ReceptorⅡ： IgG Fc Fusion Protein for injection, 0.4 mg/kg, twice weekly. After three months, the dosage was adjusted according to the state of illness. If clinical effect was better, the dosage was adjusted once weekly. The patients in two groups were treated for 6 months. After treatment, the efficacy was evaluated, and the changes of TNF-α, CRP, IL-1β, MMP-3,β-CTx, ALP, WBC, ESR, and PLT in two groups before and after treatment were compared. The changes of bone mineral density about forearm, L2- L4 lumbar normotopia and side position and the femoral Ward’s triangle in two groups were monitored.Results After treatment, the efficacies in the control and treatment groups were 68.0% and 88.0%, respectively, and there was difference between two groups （P 〈 0.05）. After treatment, the levels of TNF-α, CRP, IL-1β, MMP-3, WBC, ESR, and PLT in two groups were significantly reduced, and ALP was significantly increased, and the difference was statistically significant in the same group （P 〈 0.05）. And these indicators in treatment group improved better than those in the control group, with significant difference between two groups （P 〈 0.05）. After treatment, bone mineral density about lumbar spine normotopia and side position were significant increase, and the difference was statistically significant in the same group （P 〈 0.05）. After treatment, bone mineral density about lumbar spine normotopia and side position in treatment group were significant higher than those in the control group, with significant differences between two groups （P 〈 0.05）. Conclusion Recombinant Human Tumor Necrosis Factor-α ReceptorⅡ： IgG Fc Fusion Protein for injection has good clinical efficacy in treatment of non systemic juvenile idiopathic arthritis, and can improve osteoporosis, whose mechanism may be associated with lower levels of serum inflammatory factors.