重组人Ⅱ型肿瘤坏死因子受体-抗体Fc融合蛋白在幼年特发性关节炎治疗中临床及免疫学效应分析

Clinical and immunologic effectiveness of recombinant human necrosis factor receptor type Ⅱ-Fc fusion protein antibody in the treatment of juvenile idiopathic arthritis

目的研究重组人Ⅱ型肿瘤坏死因子(TNF)受体-抗体Fc融合蛋白治疗幼年特发性关节炎(JIA)的临床疗效及免疫学效应。方法 2011年4月至2013年8月武汉市儿童医院住院的52例非全身型JIA患儿分为治疗组32例和对照组20例。治疗组皮下注射重组人Ⅱ型TNF受体-抗体Fc融合蛋白,同时合并使用甲氨蝶呤(MTX)及非甾体类抗炎药(NSAID);对照组口服MTX,同时合并使用NSAID。治疗后1、3、6个月采用ACR Pedi评分进行疗效评估,比较放射学改变及免疫学指标改变情况。同时记录副反应。结果治疗组治疗后1个月ACR Pedi 30,治疗后3个月、6个月ACR Pedi 30、50、70达标率均显著高于对照组(P<0.05)。治疗组治疗后1个月、3个月、6个月的CRP、ESR均较治疗前明显降低(P<0.05);治疗后6个月的CD4、CD4/CD8、TNF-α、基质溶解素3(MMP-3)、Ig G、Ig M、Ig A较治疗前及对照组均降低(P<0.05);CD8、CD16CD56、CD4CD25、IL-10、转化生长因子-β(TGF-β)则较治疗前升高(P<0.05);治疗后6个月的Poznanski值较治疗前明显改善(P<0.05)。治疗后1个月、3个月治疗组CRP、ESR较对照组明显降低(P<0.05),治疗后6个月治疗组CRP较对照组明显降低(P<0.05),放射学改变较对照组轻(P<0.05)。治疗后6个月治疗组,CD4CD25、IL-10、TGF-β较对照组升高(P<0.05)。结论重组人Ⅱ型TNF受体-抗体Fc融合蛋白联合传统药物治疗非全身型JIA具有良好的安全性和有效性,临床疗效优于单纯传统治疗,能更快、更有效降低炎性指标,并能减轻放射学改变,明显改善JIA细胞及体液免疫紊乱。

Objective To evaluate the clinical and immunologic effectiveness of recombinant human necrosis factor re- ceptor type Ⅱ -Fc fusion protein antibody（rhTNFR： Fc） in the treatment of juvenile idiopathic arthritis, Methods Fif- ty-two non-systemic JIA subjects were included into this study. All JIA patients were divided into treatment and control groups randomly. The treatment group consisted of thirty-two patients on a regimen of rhTNFR：Fc subcutaneously inject- ed, permitting to combine NSAID and MTX. The control group contained twenty patients on a regimen of MTX orally tak- en, permitting to combine NSAID. Follow-up was conducted at baseline, 1 month, 3 months and 6 months after treat- ment. Clinical efficacy was evaluated based on ACR Pedi 30/50/70 score. The changes of radiographic progression and changes of immunological indexes after treatment were compared. Side effects were recorded. Results In the treatment group, at 1 month after treatment, the ACR Pedi 30 compliance rate was higher than that in the control group （P 〈 0.05）. At 3 months and 6 months, the ACR Pedi 30/50/70 compliance rates were higher than those in the control group （all P 〈 0.05）.In the treatment group, at 1 month, 3 months and 6 months after treatment, the values of CRP and ESR were lower than pretherapy （all P〈0.05）. At 6 months after treat- ment, the values of CD4, CDJCD8, TNF-α, MMP-3, IgG, IgM and IgA were lower than pretherapy （all P〈 0.05） , while the values of CDs, CD16CD56, CD4CD25, IL-10 and TGF-β were higher than pretherapy （all P 〈 0.05 ） ;the value of Poznanski was ameliorated than pretherapy （P 〈 0.05 ）. In the treatment group, at 1 month and 3 months after treatment, the values of CRP and ESR were lower than those in the control group （all P 〈 0.05 ）. At 6 months, the value of CRP was lower than that in the control group （P 〈 0.05 ） ; the radio- graphic damage was slighter than that in the control group （P 〈 0.05） ; the values of CD4, CD4/CDs, TNF-α, MMP-3, IgG, IgM and IgA were lower than those in the control group （all P〈 0.05） , while the values of CD4CD25, IL-10 and TGF-β were higher than those in the control group （all P 〈 0.05）. Conclusion Recombinant human necrosis factor re- ceptor type Ⅱ-Fc fusion protein antibody is safe and has a favorable effect in the treatment for non-systemic JIA. The clinical efficacy is superior to traditional therapy, and the inflammatory indexes decrease faster and more effective, mean- while, it can ameliorate the radiographic progression and obviously improve the cell and humoral immunity disorder in JIA.