An Oral Spleen Tyrosine Kinase (Syk) Inhibitor for Rheumatoid Arthritis.
An Oral Spleen Tyrosine Kinase (Syk) Inhibitor for Rheumatoid Arthritis.
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DOI：
10.1056/nejmoa1000500
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发表时间：
2010-09-30
影响因子：
158.5
通讯作者：
Magilavy, Daniel B.
中科院分区：
文献类型：
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作者：
Weinblatt, Michael E.;Kavanaugh, Arthur;Magilavy, Daniel B.
背景：脾酪氨酸激酶（Syk）是一种重要的免疫信号调节剂。这项2期研究的目的是评估口服Syk抑制剂R788在活动性类风湿关节炎患者中的有效性和安全性，尽管有甲氨蝶呤治疗。方法：在一项为期6个月的双盲安慰剂对照试验中，我们招募了457名长期接受甲氨蝶呤治疗的活动性类风湿关节炎患者。主要终点是第6个月的美国风湿病学会（ACR） 20反应（表明触痛和肿胀关节的数量至少减少20%，其他5项标准中的至少3项得到改善）。结果：R788, 100mg，每日2次，150mg，每日1次，在第6个月显著优于安慰剂(ACR 20应答率分别为67%和57%，vs. 35%
Background: Spleen tyrosine kinase (Syk) is an important modulator of immune signaling. The objective of this phase 2 study was to evaluate the efficacy and safety of R788, an oral inhibitor of Syk, in patients with active rheumatoid arthritis despite methotrexate therapy.Methods: We enrolled 457 patients who had active rheumatoid arthritis despite long-term methotrexate therapy in a 6-month, double-blind, placebo-controlled trial. The primary outcome was the American College of Rheumatology (ACR) 20 response (which indicates at least a 20% reduction in the number of both tender and swollen joints and improvement in at least three of five other criteria) at month 6.Results: R788, at a dose of 100 mg twice daily and at a dose of 150 mg once daily, was significantly superior to placebo at month 6 (ACR 20 response rates of 67% and 57%, respectively, vs. 35%; P