CAJ | 학술논문

目的探讨重组人细胞毒T淋巴细胞相关抗原(CTLA)-4抗体融合蛋白(rhCTLA-4Ig)治疗类风湿关节炎(RA)患者的临床疗效和安全性,及其对血清肿瘤坏死因子(TNF)-α和趋化因子CX3CL1水平的影响.方法 44例中重度RA患者随机分为rhCTLA-4Ig治疗组和安慰剂组,应用美国风湿病学会( ACR )20/50/70疗效标准和28个关节的疾病活动度评分(DAS28)评估临床疗效,并观察用药前后血清TNF-α和趋化因子CX3CL1水平.采用t检验和x2检验进行统计分析.结果治疗12周后,rhCTLA-4Ig治疗组RA患者达到ACR20、ACR50、ACR70的比率分别为95％(20/21)、76％( 16/21)和19％(4/21),而安慰剂组无一例达到ACR20、ACR50、ACR70标准,2组ACR20及ACR50缓解率比较差异有统计学意义(x2=39.17,26.69,P均＜0.01).rhCTLA-4Ig治疗组DAS28由基线的6.2±1.1降至3.1±1.3 (P＜0.01),健康状况问卷(HAQ)评分由基线的1.4±0.5降至0.4±0.5 (P＜0.01)；而安慰剂组DAS28评分治疗前后差异无统计学意义(分别为6.0±0.7,5.8±1.2,P＞0.05),HAQ评分治疗前后差异无统计学意义(分别为1.6±0.4,1.6±0.6,P＞0.05).RA患者TNF-α和CX3CL1水平明显高于健康对照组(P＜0.01),经rhCTLA-4Ig治疗12周后,rhCTLA-4Ig组血清TNF-α和CX3CL1水平明显下降(P＜0.01),而安慰剂组治疗前后差异无统计学意义(P＞0.05).结论 rhCTLA4-Ig治疗RA能够显著减低疾病活动度、改善关节功能,且耐受性良好,可明显减低血清TNF-α和趋化因子CX3CL1水平.
목적 탐토중조인세포독T림파세포상관항원(CTLA)-4항체융합단백(rhCTLA-4Ig)치료류풍습관절염(RA)환자적림상료효화안전성,급기대혈청종류배사인자(TNF)-α화추화인자CX3CL1수평적영향.방법 44례중중도RA환자수궤분위rhCTLA-4Ig치료조화안위제조,응용미국풍습병학회( ACR )20/50/70료효표준화28개관절적질병활동도평분(DAS28)평고림상료효,병관찰용약전후혈청TNF-α화추화인자CX3CL1수평.채용t검험화x2검험진행통계분석.결과 치료12주후,rhCTLA-4Ig치료조RA환자체도ACR20、ACR50、ACR70적비솔분별위95％(20/21)、76％( 16/21)화19％(4/21),이안위제조무일례체도ACR20、ACR50、ACR70표준,2조ACR20급ACR50완해솔비교차이유통계학의의(x2=39.17,26.69,P균＜0.01).rhCTLA-4Ig치료조DAS28유기선적6.2±1.1강지3.1±1.3 (P＜0.01),건강상황문권(HAQ)평분유기선적1.4±0.5강지0.4±0.5 (P＜0.01)；이안위제조DAS28평분치료전후차이무통계학의의(분별위6.0±0.7,5.8±1.2,P＞0.05),HAQ평분치료전후차이무통계학의의(분별위1.6±0.4,1.6±0.6,P＞0.05).RA환자TNF-α화CX3CL1수평명현고우건강대조조(P＜0.01),경rhCTLA-4Ig치료12주후,rhCTLA-4Ig조혈청TNF-α화CX3CL1수평명현하강(P＜0.01),이안위제조치료전후차이무통계학의의(P＞0.05).결론 rhCTLA4-Ig치료RA능구현저감저질병활동도、개선관절공능,차내수성량호,가명현감저혈청TNF-α화추화인자CX3CL1수평.
Objective To evaluate the efficacy,safety and impact of recombinant human cytotoxic T lymphocyte-associated antigen (CTLA)-4 fusion proteins (rhCTLA-4Ig) on serum human tumor necrosis factor (TNF)-α and CX3CL1 in active rheumatoid arthritis (RA) patients.Methods Forty-four RA patients were treated with rhCTLA-4Ig and placebo.Clinical response was assessed by American College of Rheumatology (ACR) criteria and disease activity score in 28 joints (DAS28).The levels of serum TNF-α and CX3CL1 were determined in 44 RA patients and 20 healthy controls by enzyme-linked immunosorbent assay (ELISA).Comparisons between groups were performed by t-test or x2 test.Results At week 12,ACR20,ACR50and ACR70 responses in RA patients with rhCTLA-4Ig were achieved by 95％(20/21 ),76％( 16/21 )and 19％(4/21) respectively,but no patient with placebo achieved ACR20,ACRS0 and ACR70 responses.There were significantly statistical differences in ACR20 and ACR50 responses (x2=39.17,26.69,P＜0.01 ).At week 12,the mean DAS28 in the rhCTLA4Ig group was 3.1±1.3 versus 6.2±1.1 at baseline (P＜0.01).Similarly,health assessment questionnaire (HAQ) improved significantly,declining from 1.4±0.5 at baseline to 0.4±0.5 at week 12 (P＜0.01).However,the mean DAS28 in the placebo group was 5.8±1.2 versus 6.0±0.7 at baseline (P＞0.05),HAQ declined from 1.6±0.4 to 1.6±0.6 (P＞0.05).In addition,there were higher levels of TNF-α and CX3CL1 in the active RA patients than those of the healthy controls (P＜0.01).After 12 weeks therapy,Serum TNF-α and CX3CL1 levels in the rhCTLA-4Ig group decreased significantly (P＜0.01).There weren't decline in the placebo group (P＞0.05).Conclusion This study has shown that rhCTLA-4Ig is very effective in reducing disease activity,improving function during the 12 weeks treatment.rhCTLA-4Ig therapy for 12 weeks can lead to significant decrease of serum TNF-α and CX3CL1.