建立在 DMARD 失败后对有明确类风湿关节炎的患者用 MTX 单药治疗的反应的临床遗传药理学模型。
Clinical pharmacogenetic model to predict response of MTX monotherapy in patients with established rheumatoid arthritis after DMARD failure.
机构信息
Radboud University Nijmegen Medical Center, PO Box 9101, 6500HB Nijmegen, The Netherlands.
出版信息
Pharmacogenomics. 2012 Jul;13(9):1087-94. doi: 10.2217/pgs.12.83.
BACKGROUND
The performance of a clinical pharmacogenetic model to predict nonresponse of methotrexate (MTX) monotherapy in patients with established rheumatoid arthritis (RA) and failure of disease-modifying antirheumatic drugs (DMARDs) was studied.
METHODS
For 75 RA patients receiving MTX monotherapy for 6 months, DNA and clinical data were available. Risk scores for nonresponse at 6 months (disease activity score >2.4), were calculated using the pharmacogenetic prediction model utilizing four clinical factors and four polymorphisms in the genes MTHFD1, AMPD1, ITPA and ATIC.
RESULTS
At 6 months, there were 25 responders and 50 nonresponders. Using the clinical pharmacogenetic prediction model, 75% (56 out of 75) were categorized into predicted responders (risk score ≤ 3.5) and predicted nonresponders (risk score ≥ 6). At 6 months, the negative predictive value was 81% (21 out of 26) and the positive predictive value was 47% (14 out of 30).
CONCLUSION
The pharmacogenetic model predicts nonresponse to MTX monotherapy, but performs better in DMARD naive recent-onset RA patients than in patients with preceding DMARD failure.
背景
研究了一种临床药物遗传学模型在预测已确诊的类风湿关节炎（RA）患者接受甲氨蝶呤（MTX）单药治疗和疾病修饰抗风湿药物（DMARDs）失败后无反应的表现。
方法
对于 75 名接受 MTX 单药治疗 6 个月的 RA 患者，可获得 DNA 和临床数据。使用药物遗传学预测模型，利用四个临床因素和 MTHFD1、AMPD1、ITPA 和 ATIC 基因中的四个多态性，计算 6 个月时无反应的风险评分（疾病活动评分>2.4）。
结果
6 个月时，有 25 名应答者和 50 名无应答者。使用临床药物遗传学预测模型，75%（75 名中的 56 名）被分为预测应答者（风险评分≤3.5）和预测无应答者（风险评分≥6）。6 个月时，阴性预测值为 81%（26 名中的 21 名），阳性预测值为 47%（30 名中的 14 名）。
结论
药物遗传学模型预测 MTX 单药治疗无反应，但在 DMARD 初治的近期发病 RA 患者中的表现优于先前 DMARD 失败的患者。
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