Section of Rheumatology, Department of Pediatrics, Children's Mercy Hospitals and Clinics, Kansas City, Missouri 64108, USA.
J Rheumatol. 2010 Apr;37(4):870-5. doi: 10.3899/jrheum.090826. Epub 2010 Mar 1.
To compare the incidence of liver toxicity and clinical response between 2 initial dosing regimens of methotrexate (MTX) for treatment of juvenile idiopathic arthritis (JIA).
Clinical and laboratory data were abstracted from the medical records of 220 children newly prescribed MTX from the same geographic region. One cohort received initial doses of MTX > 0.5 mg/kg/week ("high-dose") and one cohort received initial doses of MTX <or= 0.5 mg/kg/week ("low-dose"). Toxicity was defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) above the normal range, and positive clinical response was defined as a reduction in active joint count during the first 6 months of MTX therapy.
One hundred twenty-six children were in the high-dose MTX group, 94 in the low-dose MTX group. At 6 months, the high-dose group was more likely to have an elevated AST or ALT (adjusted OR 3.89, 95% CI 1.82-8.29, p < 0.0001). Subjects receiving both MTX and nonsteroidal antiinflammatory drugs (NSAID) had no significant difference between groups in change of active joint count, while subjects in the high-dose group but not taking NSAID had more active joints (p = 0.036) at 6 months compared to the low-dose group.
Initial high-dose MTX was associated with an increased risk of at least one liver enzyme abnormality with no significant improvement in active joint count. This suggests that there is no apparent benefit, while the potential for liver toxicity is increased, when using higher doses of MTX at treatment inception in patients with JIA.
比较两种甲氨蝶呤（MTX）起始剂量方案治疗幼年特发性关节炎（JIA）的肝毒性发生率和临床疗效。
从同一地理区域新处方 MTX 的 220 名儿童的病历中提取临床和实验室数据。一组接受初始剂量 MTX > 0.5 mg/kg/周（“高剂量”），另一组接受初始剂量 MTX ≤ 0.5 mg/kg/周（“低剂量”）。毒性定义为天门冬氨酸氨基转移酶（AST）和/或丙氨酸氨基转移酶（ALT）高于正常范围，阳性临床疗效定义为 MTX 治疗的前 6 个月内活跃关节计数减少。
126 名儿童在高剂量 MTX 组，94 名在低剂量 MTX 组。在 6 个月时，高剂量组更有可能出现 AST 或 ALT 升高（调整后的 OR 3.89，95%CI 1.82-8.29，p < 0.0001）。同时接受 MTX 和非甾体抗炎药（NSAID）的受试者在活跃关节计数变化方面两组间无显著差异，而未服用 NSAID 的高剂量组受试者在 6 个月时的活跃关节数（p = 0.036）较低剂量组更多。
初始高剂量 MTX 与至少一种肝酶异常风险增加相关，而在 JIA 患者治疗起始时使用更高剂量的 MTX 并没有显著改善活跃关节计数。这表明，在使用更高剂量的 MTX 时，没有明显的获益，而肝毒性的风险增加。
