Tofacitinib or Adalimumab versus Placebo in Rheumatoid Arthritis
Tofacitinib or Adalimumab versus Placebo in Rheumatoid Arthritis
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DOI：
10.1056/nejmoa1112072
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发表时间：
2012-08-09
影响因子：
158.5
通讯作者：
Wilkinson, Bethanie
中科院分区：
文献类型：
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作者：
van Vollenhoven, Ronald F.;Fleischmann, Roy;Wilkinson, Bethanie
托法替尼（cp - 690550）是一种新型口服Janus激酶抑制剂，正在研究用于治疗类风湿性关节炎。方法在这项为期12个月的3期临床试验中，717名接受稳定剂量甲氨蝶呤治疗的患者被随机分配到5 mg托法替尼每日2次、10 mg托法替尼每日2次、40 mg阿达木单抗每2周1次或安慰剂组。在第3个月，安慰剂组中肿胀和压痛关节的数量没有从基线减少20%的患者以盲法方式切换到每天两次的5 mg或10 mg托法替尼；在第6个月，所有仍然接受安慰剂的患者以盲法方式切换到托法替尼。三个主要结局指标为：第6个月时美国风湿病学会评分（acr20）改善20%；健康评估问卷-残疾指数（HAQ-DI）得分从基线到第3个月的变化（范围从0到3，得分越高表明残疾程度越严重）；第6个月基于红细胞沉降率（DAS28-4[ESR]）的28个关节计数的疾病活动性评分低于2.6的患者百分比（评分范围从0到9.4，得分越高表明疾病活动性越强）。结果在第6个月，接受5 mg或10 mg托法替尼组（分别为51.5%和52.6%）和阿达木单抗组（47.2%）的ACR 20缓解率高于接受安慰剂组（28.3%）（P < 0.05）
BACKGROUNDTofacitinib (CP-690,550) is a novel oral Janus kinase inhibitor that is being investigated for the treatment of rheumatoid arthritis.METHODSIn this 12-month, phase 3 trial, 717 patients who were receiving stable doses of methotrexate were randomly assigned to 5 mg of tofacitinib twice daily, 10 mg of tofacitinib twice daily, 40 mg of adalimumab once every 2 weeks, or placebo. At month 3, patients in the placebo group who did not have a 20% reduction from baseline in the number of swollen and tender joints were switched in a blinded fashion to either 5 mg or 10 mg of tofacitinib twice daily; at month 6, all patients still receiving placebo were switched to tofacitinib in a blinded fashion. The three primary outcome measures were a 20% improvement at month 6 in the American College of Rheumatology scale (ACR 20); the change from baseline to month 3 in the score on the Health Assessment Questionnaire-Disability Index (HAQ-DI) (which ranges from 0 to 3, with higher scores indicating greater disability); and the percentage of patients at month 6 who had a Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-4[ESR]) of less than 2.6 (with scores ranging from 0 to 9.4 and higher scores indicating greater disease activity).RESULTSAt month 6, ACR 20 response rates were higher among patients receiving 5 mg or 10 mg of tofacitinib (51.5% and 52.6%, respectively) and among those receiving adalimumab (47.2%) than among those receiving placebo (28.3%) (P