多聚谷氨酸化甲氨蝶呤与类风湿关节炎疗效和不良反应的相关性研究进展

Progress in Correlation of Methotrexate Polyglutamates in Erythrocytes with Efficacy and Adverse Reactions of Methotrexate in Rheumatoid Arthritis

甲氨蝶呤(MTX)是治疗类风湿关节炎(RA)的首选药物,但20%~40%的RA患者服用MTX无效。MTX的血浆半衰期短,其浓度与疗效无相关性。MTX在红细胞、滑膜细胞等细胞内转化为多聚谷氨酸化甲氨蝶呤(MTXPGs),在细胞内的滞留时间较长,且与叶酸途径中关键酶的亲和力更强、抗炎作用也更强,因此选用红细胞内MTXPGs浓度来预测治疗效果及安全性成为目前研究的重点。综述MTXPGs与RA疗效和不良反应的相关性研究进展,并对影响MTX作用的相关因素进行分析,为临床合理用药提供参考。

Methotrexate（MTX） is the first-line therapy for rheumatoid arthritis（RA） although 20% - 40% patients fail to have adequate clinical response. Plasma MTX concentrations fall rapidly and is not correlated with drug efficacy. In some cells like erythrocytes and synovial cells, MTX is converted to methotrexate polyglutamates（MTXPGs） which have prolonged intracellular retention, higher affinity to key enzymes in folate pathways and thus stronger anti-inflammatory effect. Therefore, the option of using MTXPGs in erythrocytes to predict drug efficacy and safety has become the focus of current research. In this article, the progress in correlation of MTXPGs with drug efficacy and adverse reactions was reviewed, and the determinants of MTX effect was analyzed, so as to provide reference for rational drug use.