多聚谷氨酸化甲氨蝶呤浓度与类风湿关节炎临床疗效及肝毒性之间的相关性

Correlation of methotrexate polyglutamates concentration with clinical efficacy and hepatotoxicity in patients with rheumatoid arthritis

目的研究口服小剂量甲氨蝶呤(MTX)的类风湿关节炎(RA)患者红细胞中多聚谷氨酸化甲氨蝶呤(MTXPGs)浓度与临床疗效及肝毒性之间的相关性。方法前瞻性收集医院128例接受小剂量MTX治疗的RA患者,观察其疗效和不良反应;采用LC-MS/MS法检测患者红细胞中MTXPGs浓度,使用SPSS软件分析MTXPGs浓度与疗效及肝毒性的相关性。结果94例(73.4%)患者治疗有效,34例(26.6%)患者治疗无效,其中16例(12.5%)患者发生肝毒性。Mann-Whitney U检验结果显示,有效组与无效组的MTXPGs浓度差异有统计学意义(U=1320,P<0.01),发生肝毒性组与未发生肝毒性组MTXPGs浓度有统计学意义(U=544,P<0.05)。ROC分析显示,当ΔDAS28>1.2时,MTXPGs浓度的临界值为25μg·L^(-1)(P<0.001);当AST或ALT超过正常值上限时,MTXPGs浓度的临界值为38μg·L^(-1)(P<0.05)。说明当浓度范围为25~38μg·L^(-1)时,患者疗效好且肝毒性小。结论红细胞中MTXPGs浓度与RA患者临床疗效及肝毒性间存在相关性,临床药师有必要通过监测MTXPGs浓度来指导临床合理用药。

AIM To study the correlation of methotrexate polyglutamates(MTXPGs)concentration in erythrocytes with clinical efficacy and hepatotoxicity in patients with rheumatoid arthritis(RA)orally taking low-dose methotrexate(MTX).METHODS Totally 128 RA patients receiving low dose MTX were prospectively collected to observe the efficacy and adverse reactions.The concentration of MTXPGs in erythrocytes was detected by LC-MS/MS,and the correlation between MTXPGs concentration and efficacy and hepatotoxicity was analyzed by SPSS software.RESULTS 94 patients(73.4%)were effective and 34(26.6%)were ineffective,and 16 patients(12.5%)developed hepatotoxicity.Mann-whitney U test results showed that the concentrations of MTXPGs in the effective group and the ineffective group were significantly different(U=1320,P<0.01),and the concentrations of MTXPGs in the hepatotoxicity group and the non-hepatotoxicity group were significantly different(U=544,P<0.05).ROC analysis showed that whenΔDAS28>1.2,the critical value of MTXPGs concentration was 25μg·L^(-1)(P<0.001);and when AST or ALT exceeded the upper limit of normal value,the critical value of MTXPGs concentration was 38μg·L^(-1)(P<0.05).The results indicated that when the concentration range was 25-38μg·L^(-1),the patients had good effect and low hepatotoxicity.CONCLUSION There is a correlation between the concentration of MTXPGs in erythrocytes and the clinical efficacy and hepatotoxicity of RA patients,so it is necessary to monitor the concentration of MTXPGs to guide clinical rational drug use.