Tofacitinib versus Methotrexate in Rheumatoid Arthritis
Tofacitinib versus Methotrexate in Rheumatoid Arthritis
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DOI：
10.1056/nejmoa1310476
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发表时间：
2014-06-19
影响因子：
158.5
通讯作者：
van Vollenhoven, Ronald F.
中科院分区：
文献类型：
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作者：
Lee, Eun Bong;Fleischmann, Roy;van Vollenhoven, Ronald F.
背景甲氨蝶呤是最常用的一线抗风湿药物。我们报告了一项口服Janus激酶抑制剂托法替尼单药治疗的3期研究结果，方法我们将958名患者随机分为两组，一组接受5 mg或10 mg托法替尼，每日两次，另一组接受甲氨蝶呤，剂量递增至20 mg/d。8周以上; 956例患者接受了研究药物治疗。第6个月时的共同主要终点是货车der Heijde改良总Sharp评分较基线的平均变化（其范围从0到448，评分越高，表明结构性关节损伤越大）和美国流变学学会（ACR）70应答的患者比例（压痛和肿胀关节数量减少>= 70%，其他五项标准中有三项改善>= 70%：患者对疼痛、残疾程度、C反应蛋白水平或红细胞沉降率的评估，患者对疾病的总体评估，结果托法替尼组从基线到第6个月的改良总Sharp评分的平均变化显著小于甲氨蝶呤组，但所有三组的变化均为适度（5 mg托法替尼组为0.2分，
BackgroundMethotrexate is the most frequently used first-line antirheumatic drug. We report the findings of a phase 3 study of monotherapy with tofacitinib, an oral Janus kinase inhibitor, as compared with methotrexate monotherapy in patients with rheumatoid arthritis who had not previously received methotrexate or therapeutic doses of methotrexate.MethodsWe randomly assigned 958 patients to receive 5 mg or 10 mg of tofacitinib twice daily or methotrexate at a dose that was incrementally increased to 20 mg per week over 8 weeks; 956 patients received a study drug. The coprimary end points at month 6 were the mean change from baseline in the van der Heijde modified total Sharp score (which ranges from 0 to 448, with higher scores indicating greater structural joint damage) and the proportion of patients with an American College of Rheumatology (ACR) 70 response (>= 70% reduction in the number of both tender and swollen joints and >= 70% improvement in three of five other criteria: the patient's assessment of pain, level of disability, C-reactive protein level or erythrocyte sedimentation rate, global assessment of disease by the patient, and global assessment of disease by the physician).ResultsMean changes in the modified total Sharp score from baseline to month 6 were significantly smaller in the tofacitinib groups than in the methotrexate group, but changes were modest in all three groups (0.2 points in the 5-mg tofacitinib group and