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监测幼年特发性关节炎中甲氨蝶呤的毒性。

Monitoring methotrexate toxicity in juvenile idiopathic arthritis.

机构信息

Division of Rheumatology, University of Cincinnati Medical Center, Cincinnati, OH 45229-3039, USA.

出版信息

J Rheumatol. 2009 Dec;36(12):2813-8. doi: 10.3899/jrheum.090482. Epub 2009 Nov 16.

Abstract

OBJECTIVE

To determine the frequency of laboratory abnormalities with methotrexate (MTX) use in patients with juvenile idiopathic arthritis (JIA); to identify potential risk factors for MTX toxicity requiring medical interventions; and to compare the frequency of liver function abnormalities in patients treated with MTX to those not treated with MTX.

METHODS

Results of MTX surveillance laboratory testing (SLT) available in clinical databases were reviewed for 588 children with JIA. Information on demographics, JIA features, and factors previously associated with increased frequency of SLT abnormalities was obtained.

RESULTS

Results of SLT performed in at least 4-month intervals were available for 138 JIA patients whose JIA was not treated with MTX, and for 198 JIA patients treated with MTX plus folic acid. On SLT of the MTX-treated patients, there were 44 of 2650 (1.7%) AST tests and 90 of 2647 (3.4%) ALT tests that exceeded 2 times the upper limit of normal (> 2 ULN) in 30 children (15%). AST or ALT tests at > 2 ULN occurred more often with systemic JIA (p = 0.04), macrophage activation syndrome, during infections, in systemic antibiotic use, and after intensifying JIA drug regimens. AST or ALT results at > 2 ULN were as frequent among MTX-treated children as those not treated with MTX. Renal and hematological abnormalities with MTX were uncommon.

CONCLUSION

Liver enzyme abnormalities > 2 ULN are rare in JIA, irrespective of MTX exposure. These data suggest that the adult standard of SLT every 4-8 weeks may not be necessary in children treated with MTX, especially if certain risk factors are absent.

摘要

目的

确定幼年特发性关节炎(JIA)患者使用甲氨蝶呤(MTX)时实验室异常的频率;确定需要医疗干预的 MTX 毒性的潜在危险因素;并比较接受 MTX 治疗和未接受 MTX 治疗的患者肝功能异常的频率。

方法

回顾了 588 例 JIA 患儿临床数据库中可获得的 MTX 监测实验室检测(SLT)结果。获取了人口统计学、JIA 特征以及与 SLT 异常频率增加相关的因素的信息。

结果

对未接受 MTX 治疗的 138 例 JIA 患者和接受 MTX+叶酸治疗的 198 例 JIA 患者进行了至少 4 个月间隔的 SLT。在接受 MTX 治疗的患者中,有 30 名儿童(15%)的 2650 次 AST 检查中有 44 次和 2647 次 ALT 检查中有 90 次超过正常上限的 2 倍(>2ULN)。全身型 JIA(p=0.04)、巨噬细胞活化综合征、感染时、全身使用抗生素后以及 JIA 药物方案强化后,AST 或 ALT 检查>2ULN 更为常见。接受 MTX 治疗的儿童的 AST 或 ALT 结果>2ULN 与未接受 MTX 治疗的儿童一样频繁。MTX 引起的肾脏和血液学异常不常见。

结论

无论是否接触 MTX,JIA 患者的肝酶异常>2ULN 都很少见。这些数据表明,对于接受 MTX 治疗的儿童,成人标准的每 4-8 周进行一次 SLT 可能不是必需的,特别是如果没有某些危险因素的话。

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