Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein
Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein
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DOI：
10.1056/nejm199707173370301
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发表时间：
1997-07-17
影响因子：
158.5
通讯作者：
Blosch, CM
中科院分区：
文献类型：
--
作者：
Moreland, LW;Baumgartner, SW;Blosch, CM
背景肿瘤坏死因子是一种促炎细胞因子，参与类风湿关节炎的发病过程，拮抗肿瘤坏死因子可降低疾病的活动性。这项研究评估了一种新型的肿瘤坏死因子拮抗剂的安全性和有效性。这是一种由可溶性肿瘤坏死因子受体(P75)连接到人IgG1Fc部分(TNFR：Fc)的重组融合蛋白。方法在这项多中心双盲试验中，我们随机分配180名难治性类风湿关节炎患者接受安慰剂或三种剂量的TNFR：Fc(每平方米体表面积0.25、2或16 mg/m2)皮下注射，每周两次，持续三个月。临床疗效通过美国风湿病学会标准定义的关节炎综合症状的变化来衡量。结果TNFR：FC治疗后疾病活动性显著降低，且其疗效与剂量相关。3个月后，每平方米服用16 mg TNFR：FC的患者中，75%的患者症状改善20%或更多，而安慰剂组只有14%(P
Background Tumor necrosis factor (TNF) is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis, and antagonism of TNF may reduce the activity of the disease. This study evaluated the safety and efficacy of a novel TNF antagonist - a recombinant fusion protein that consists of the soluble TNF receptor (p75) linked to the Fc portion of human IgG1 (TNFR:Fc).Methods In this multicenter, double-blind trial, we randomly assigned 180 patients with refractory rheumatoid arthritis to receive subcutaneous injections of placebo or one of three doses of TNFR:Fc (0.25, 2, or 16 mg per square meter of body-surface area) twice weekly for three months. The clinical response was measured by changes in composite symptoms of arthritis defined according to American College of Rheumatology criteria.Results Treatment with TNFR:Fc led to significant reductions in disease activity, and the therapeutic effects of TNFR:Fc were dose-related. At th ree months, 75 percent of the patients in the group assigned to 16 mg of TNFR:Fc per square meter had improvement of 20 percent or more in symptoms, as com pared with 14 percent in the placebo group (P