A clinical pharmacogenetic model to predict the efficacy of methotrexate monotherapy in recent-onset rheumatoid arthritis
A clinical pharmacogenetic model to predict the efficacy of methotrexate monotherapy in recent-onset rheumatoid arthritis
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DOI：
10.1002/art.22640
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发表时间：
2007-06-01
影响因子：
--
通讯作者：
Guchelaar, Henk-Jan
中科院分区：
文献类型：
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作者：
Wessels, Judith A. M.;van der Kooij, Sjoerd M.;Guchelaar, Henk-Jan
Objective.建立一个临床药物遗传学模型来预测甲氨蝶呤（MTX）治疗类风湿关节炎（RA）的疗效。205例新诊断为RA和活动性疾病的患者接受MTX（开始剂量为7.5 mg/周，4周后增加至15 mg/周）和叶酸（1 mg/天）治疗。如果3个月时疾病活动评分（DAS）>2.4，则MTX剂量增加至25 mg/周。选择了24个可能影响疾病状态和药物反应的基线变量。此外，在13个基因的17个多态性与MTX的作用机制，嘌呤和嘧啶的合成，进行了测定。比较应答者（定义为DAS患者）之间的因素
Objective. To develop a clinical pharmacogenetic model to predict the efficacy of methotrexate (MTX) in rheumatoid arthritis (RA).Methods. Two hundred five patients with newly diagnosed RA and active disease were treated with MTX (initiated at a dosage of 7.5 mg/week and increased to 15 mg/week after 4 weeks) and folic acid (1 mg/day). If the Disease Activity Score (DAS) was >2.4 at 3 months, the dosage of MTX was increased up to 25 mg/week. Twenty-four baseline variables possibly influencing disease state and drug response were selected. In addition, 17 polymorphisms in 13 genes related to the MTX mechanism of action, purine and pyrimidine synthesis, were determined. Factors were compared between responders (defined as patients with a DAS