中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2010年
31期
2205-2208
,共4页
李玲%张晓%崔阳%卢奕云%王淑侠%董光富%石韫珍%罗日强%雷云霞
李玲%張曉%崔暘%盧奕雲%王淑俠%董光富%石韞珍%囉日彊%雷雲霞
리령%장효%최양%로혁운%왕숙협%동광부%석운진%라일강%뢰운하
关节炎%肿瘤坏死因子-α%骨密度
關節炎%腫瘤壞死因子-α%骨密度
관절염%종류배사인자-α%골밀도
Arthritis%TNF-alpha%Bone mineral density
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年者经益赛普治疗6个月后复查X线已愈合并拆除内固定钢板.结论 益赛普和传统DMARD均能明显降低TNF-α、IL-1β、ESR、CRP水平,同时提升腰椎骨密度和ALP水平达到控制炎症的作用,益赛普治疗对急性时相指标及骨代谢指标的改善早于传统DMARD,从而更早改善病情,减少骨破坏.
目的 觀察重組人Ⅱ型腫瘤壞死因子受體-抗體Fc融閤蛋白對幼年特髮性關節炎(JIA)患者細胞因子和骨代謝的影響.方法 採用前瞻性、非隨機、對照、開放研究.納入自2006年12月至2009年6月廣東省人民醫院診治的活動性JIA患者,共31例,年齡平均(12.7±2.3)歲.研究第1階段(0～3箇月),根據患者經濟情況分彆納入實驗組和對照組治療.兩組患者在病程、年齡、性彆等方麵匹配.試驗組的給藥方案為重組人Ⅱ型腫瘤壞死因子受體-抗體Fc融閤蛋白(益賽普)0.4 mg/kg,皮下註射,2次/週,患者共18例,其中附著點炎型15例,多關節炎型2例,全身型1例;對照組給藥方案為甲氨蝶呤10 mg·m-2·週-1,2例不能耐受者換用柳氮磺胺吡啶(SASP)30～50mg·kg-1·d-1,患者共13例(附著點炎型9例,多關節炎型2例,全身型2例),兩組多關節炎型和全身型患者允許使用穩定劑量的非甾類抗炎藥(NSAID)或小劑量糖皮質激素.第2階段(3～6箇月),有效者繼續原治療,試驗組益賽普減量為0.4 mg·kg-1·週-1,閤併外週關節炎或治療無效者可以加用SASP.分彆在治療前和1、3及6箇月隨訪.觀察腫瘤壞死因子-α(TNF-α)、基質金屬蛋白酶-3(MMP-3)、白細胞介素-1β(IL-1β)、骨鈣素、β-膠原分解片斷(β-CTx)、堿性燐痠酶(ALP)、紅細胞沉降率(ESR)、C反應蛋白(CRP)和骨密度的動態變化.結果 兩組ALP、腰椎正側位骨密度隨治療明顯升高,TNF-α、IL-1β、ESR、CRP隨治療延長明顯下降(P<0.05).治療1箇月後兩組間ESR分彆為(16±8)mm/h比(60±38)mm/h,CRP分彆為(10±7)mg/L比(47±37)mg/L,β-CTx分彆為2.1±0.8 vs 1.1±0.9μg/L,差異有統計學意義.兩組骨鈣素逐漸增加,且試驗組高于對照組;MMP-3有下降趨勢,但組間和各時間點的差異無統計學意義.股骨Ward's三角區和前臂骨骨密度均無明顯變化.其中1例骨摺不愈閤達2年者經益賽普治療6箇月後複查X線已愈閤併拆除內固定鋼闆.結論 益賽普和傳統DMARD均能明顯降低TNF-α、IL-1β、ESR、CRP水平,同時提升腰椎骨密度和ALP水平達到控製炎癥的作用,益賽普治療對急性時相指標及骨代謝指標的改善早于傳統DMARD,從而更早改善病情,減少骨破壞.
목적 관찰중조인Ⅱ형종류배사인자수체-항체Fc융합단백대유년특발성관절염(JIA)환자세포인자화골대사적영향.방법 채용전첨성、비수궤、대조、개방연구.납입자2006년12월지2009년6월광동성인민의원진치적활동성JIA환자,공31례,년령평균(12.7±2.3)세.연구제1계단(0～3개월),근거환자경제정황분별납입실험조화대조조치료.량조환자재병정、년령、성별등방면필배.시험조적급약방안위중조인Ⅱ형종류배사인자수체-항체Fc융합단백(익새보)0.4 mg/kg,피하주사,2차/주,환자공18례,기중부착점염형15례,다관절염형2례,전신형1례;대조조급약방안위갑안접령10 mg·m-2·주-1,2례불능내수자환용류담광알필정(SASP)30～50mg·kg-1·d-1,환자공13례(부착점염형9례,다관절염형2례,전신형2례),량조다관절염형화전신형환자윤허사용은정제량적비치류항염약(NSAID)혹소제량당피질격소.제2계단(3～6개월),유효자계속원치료,시험조익새보감량위0.4 mg·kg-1·주-1,합병외주관절염혹치료무효자가이가용SASP.분별재치료전화1、3급6개월수방.관찰종류배사인자-α(TNF-α)、기질금속단백매-3(MMP-3)、백세포개소-1β(IL-1β)、골개소、β-효원분해편단(β-CTx)、감성린산매(ALP)、홍세포침강솔(ESR)、C반응단백(CRP)화골밀도적동태변화.결과 량조ALP、요추정측위골밀도수치료명현승고,TNF-α、IL-1β、ESR、CRP수치료연장명현하강(P<0.05).치료1개월후량조간ESR분별위(16±8)mm/h비(60±38)mm/h,CRP분별위(10±7)mg/L비(47±37)mg/L,β-CTx분별위2.1±0.8 vs 1.1±0.9μg/L,차이유통계학의의.량조골개소축점증가,차시험조고우대조조;MMP-3유하강추세,단조간화각시간점적차이무통계학의의.고골Ward's삼각구화전비골골밀도균무명현변화.기중1례골절불유합체2년자경익새보치료6개월후복사X선이유합병탁제내고정강판.결론 익새보화전통DMARD균능명현강저TNF-α、IL-1β、ESR、CRP수평,동시제승요추골밀도화ALP수평체도공제염증적작용,익새보치료대급성시상지표급골대사지표적개선조우전통DMARD,종이경조개선병정,감소골파배.
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 vs 47 ±37 mg/Land β-CTx 2.1±0.8 vs 1.1±0.9 μg/L at 1 month in two groups respectively with statistic difference ( P<0.05).BGP increased and MMP-3 decreased in both groups with no statistic difference.Femur Ward's triangular area and forearm bone mineral density had no statistic difference between two groups.Interestingly,one case with bone fracture for two years has healed after a 6-month therapy of rhTNFR:Fc as proved by X-ray.Conclusion Both rhTNFR:Fc and traditional DMARDs both can reduce the levels of TNF-α,IL-1β,ESR and CRP and increase lumbar spine bone mineral density and ALP significantly.RhTNFR:Fc improves the acute phase index and bone metabolism index earlier than the traditional therapy.Thus disease and bone destruction are controlled more earlier.
