重组人Ⅱ型肿瘤坏死因子受体-抗体Fc融合蛋白对幼年特发性关节炎患者细胞因子和骨代谢的影响  

Effect of recombinant human tumor necrosis factor receptor type Ⅱ - Fc fusion protein antibody on cytokines and bone metabolism in patients with juvenile idiopathic arthritis

作　　者：李玲[1] 张晓[1] 崔阳[1] 卢奕云[2] 王淑侠[3] 董光富[1] 石韫珍[1] 罗日强[1] 雷云霞[1] 

机构地区：[1]广东省医学科学院广东省人民医院风湿免疫科,广州510080 [2]广东省医学科学院广东省人民医院儿科,广州510080 [3]广东省医学科学院广东省人民医院核医学科,广州510080

出　　处：《中华医学杂志》2010年第31期2205-2208,共4页National Medical Journal of China

摘　　要：目的 观察重组人Ⅱ型肿瘤坏死因子受体-抗体Fc融合蛋白对幼年特发性关节炎（JIA）患者细胞因子和骨代谢的影响.方法 采用前瞻性、非随机、对照、开放研究.纳入自2006年12月至2009年6月广东省人民医院诊治的活动性JIA患者,共31例,年龄平均（12.7±2.3）岁.研究第1阶段（0～3个月）,根据患者经济情况分别纳入实验组和对照组治疗.两组患者在病程、年龄、性别等方面匹配.试验组的给药方案为重组人Ⅱ型肿瘤坏死因子受体-抗体Fc融合蛋白（益赛普）0.4 mg/kg,皮下注射,2次/周,患者共18例,其中附着点炎型15例,多关节炎型2例,全身型1例 对照组给药方案为甲氨蝶呤10 mg·m-2·周-1,2例不能耐受者换用柳氮磺胺吡啶（SASP）30～50mg·kg-1·d-1,患者共13例（附着点炎型9例,多关节炎型2例,全身型2例）,两组多关节炎型和全身型患者允许使用稳定剂量的非甾类抗炎药（NSAID）或小剂量糖皮质激素.第2阶段（3～6个月）,有效者继续原治疗,试验组益赛普减量为0.4 mg·kg-1·周-1,合并外周关节炎或治疗无效者可以加用SASP.分别在治疗前和1、3及6个月随访.观察肿瘤坏死因子-α（TNF-α）、基质金属蛋白酶-3（MMP-3）、白细胞介素-1β（IL-1β）、骨钙素、β-胶原分解片断（β-CTx）、碱性磷酸酶（ALP）、红细胞沉降率（ESR）、C反应蛋白（CRP）和骨密度的动态变化.结果 两组ALP、腰椎正侧位骨密度随治疗明显升高,TNF-α、IL-1β、ESR、CRP随治疗延长明显下降（P〈0.05）.治疗1个月后两组间ESR分别为（16±8）mm/h比（60±38）mm/h,CRP分别为（10±7）mg/L比（47±37）mg/L,β-CTx分别为2.1±0.8 vs 1.1±0.9μg/L,差异有统计学意义.两组骨钙素逐渐增加,且试验组高于对照组 MMP-3有下降趋势,但组间和各时间点的差异无统计学意义.股骨Ward＇s三角区和前臂骨骨密度均无明显变化.其中1例骨折不愈合达2年者经益赛普治Objective To evaluate the influence of the recombinant human type Ⅱ tumor necrosis factor receptor-antibody Fc fusion protein （rhTNFR：Fc） on cytokines and bone metabolism in patients with juvenile idiopathic arthritis （JIA）.Methods This was a prospective,non-randomized,controlled and openlabel study.Thirty-one patients with JIA in active state were enrolled at our hospital from December 2006 to June 2009.The mean age was 12.7±2.3 years.Exclusive criteria included infection with tuberculosis and hepatitis B etc.,abnormal renal or hepatic function.Study consists of two phases.During the first phase （0-3 months）,according to the economic status,all JIA patients were divided into treatment and control groups.The treatment group consisted of 18 patients （enthesitis-related arthritis,n = 15 polyarticular-onset arthritis,n =2 systemic-onset type,n = 1 ） on a regimen of rhTNFR：Fc 0.4 mg/kg,subcutaneously injected twice weekly.The control group contained 13 patients （enthesitis-related arthritis,n = 9 polyarticular-onset arthritis,n=2 systemic-onset type,n =2） on a regimen of MTX 10 mg·m-2·w-1 Two intolerance patients were given suffasalazine （SASP） 30-50 mg·kg-1·d-1.During the second phase （3-6 months）,the responding patients continued the original therapy.The rhTNFR：Fc group received a reduced dosage of 0.4 mg·kg- 1 ·w-1.All patients of both groups who became complicated with peripheral arthritis or were non-responding had the addition of SASP.Follow-up was conducted at baseline,1 month,3months and 6 months.And TNF-α,MMP-3,IL-1β,osteocalcin （BGP）,β-collagen fragment （β-CTx）,alkaline phosphatase,erythrocyte sedimentation rate （ESR）,c-reactive protein （CRP） and bone mineral density dynamic changes were examined respectively in the treatment process.Results Alkaline pbosphatase and lumbar spine bone mineral density increased while TNF-α,IL-1β,ESR and CRP decreased significantly in two groups （P〈0.05）.ESR were 16±8.0 mm/h vs 60±38 mm/h,CRP 10±7 mg/L v

关 键 词：关节炎 肿瘤坏死因子-Α 骨密度 

分 类 号：R725.9[医药卫生—儿科]