Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial
Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial
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DOI：
10.1016/s0140-6736(12)61424-x
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发表时间：
2013-02-09
期刊：
影响因子：
168.9
通讯作者：
Mebus, Charles
中科院分区：
文献类型：
--
作者：
Burmester, Gerd R.;Blanco, Ricardo;Mebus, Charles
背景类风湿性关节炎是一种异质性慢性疾病，目前还没有发现对所有患者普遍且持久有效的治疗药物。我们研究了托法替布 (CP-690,550)（一种新型口服 Janus 激酶抑制剂）作为类风湿性关节炎的靶向免疫调节剂和疾病修饰疗法的有效性。方法我们在北美、欧洲和拉丁美洲等 13 个国家的 82 个中心进行了为期 6 个月的双盲平行组 3 期研究。 399 名 18 岁或以上患有中重度类风湿性关节炎且对肿瘤坏死因子抑制剂 (TNFi) 反应不足的患者通过自动互联网或电话系统以 2:2:1:1 的比例随机分配，接受每天两次的治疗：托法替布 5 mg（n=133）；托法替布 10 mg (n=134)；或安慰剂 (n=132)，均含有甲氨蝶呤。在第 3 个月，给予安慰剂的患者进展为托法替布 5 mg 每天两次 (n=66) 或 10 mg 每天两次 (n=66)。主要终点包括美国风湿病学会 (ACR) 20 反应率、健康评估问卷-残疾指数 (HAQ-DI) 相对于基线的平均变化以及疾病活动评分 (DAS) 28-4(ESR) 低于 2.6 的比率（简称 DAS28）
Background Rheumatoid arthritis is a heterogeneous chronic disease, and no therapeutic agent has been identified which is universally and persistently effective in all patients. We investigated the effectiveness of tofacitinib (CP-690,550), a novel oral Janus kinase inhibitor, as a targeted immunomodulator and disease-modifying therapy for rheumatoid arthritis.Methods We did a 6-month, double-blind, parallel-group phase 3 study at 82 centres in 13 countries, including North America, Europe, and Latin America. 399 patients aged 18 years or older with moderate-to-severe rheumatoid arthritis and inadequate response to tumour necrosis factor inhibitors (TNFi) were randomly assigned in a 2: 2: 1: 1 ratio with an automated internet or telephone system to receive twice a day treatment with: tofacitinib 5 mg (n=133); tofacitinib 10 mg (n=134); or placebo (n=132), all with methotrexate. At month 3, patients given placebo advanced to either tofacitinib 5 mg twice a day (n=66) or 10 mg twice a day (n=66). Primary endpoints included American College of Rheumatology (ACR) 20 response rate, mean change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI), and rates of disease activity score (DAS) 28-4(ESR) less than 2.6 (referred to as DAS28