Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital and Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.
Clin Rheumatol. 2021 Nov;40(11):4493-4500. doi: 10.1007/s10067-021-05811-7. Epub 2021 Jun 11.
The objective of this study is to determine whether an initial methotrexate (MTX) dosage is associated with an increased risk of liver toxicity in patients with rheumatoid arthritis (RA).
This retrospective study included 730 RA patients who started MTX treatment between 2004 and 2019 at the rheumatology clinic at Seoul National University Hospital. The patients were divided into three groups according to the initial dosage of MTX they received: low (MTX ≤ 7.5 mg/week), intermediate (MTX 10-12.5 mg/week), and high (MTX ≥ 15 mg/week) dosage groups. Hepatotoxicity, defined as elevations in aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) levels more than twofold above the upper limit of normal (2 × ULN), was examined during 90 days of MTX treatment. Predictors of hepatotoxicity were identified using logistic regression analyses.
Of the 730 patients, 10 (1.4%) patients developed hepatotoxicity. The rate of hepatotoxicity was not different between the three MTX dosage groups. Univariate logistic regression analyses showed that the risk of hepatotoxicity was not higher in the intermediate MTX dosage group (odds ratio (OR): 0.89, 95% confidential interval (CI): 0.20-4.00, p = 0.877) or in the high MTX dosage group (OR: 1.23, 95% CI: 0.24-6.14, p = 0.804) than in the low MTX dosage group. Multivariate logistic regression analyses showed that elevated baseline AST and/or ALT levels above ULN and concomitant leflunomide use were associated with MTX hepatotoxicity.
The initial MTX dosage is not associated with increased hepatotoxicity in RA patients.
• An initial methotrexate (MTX) dosage is not associated with liver toxicity in patients with rheumatoid arthritis (RA). • RA patients with a baseline liver function test (LFT) abnormality or receiving concomitant leflunomide treatment should be monitored closely for LFT abnormalities during the early phase of MTX treatment.
本研究旨在确定类风湿关节炎（RA）患者初始甲氨蝶呤（MTX）剂量是否与肝毒性风险增加相关。
本回顾性研究纳入了 2004 年至 2019 年期间在首尔国立大学医院风湿病科接受 MTX 治疗的 730 例 RA 患者。根据初始 MTX 剂量将患者分为三组：低剂量（MTX≤7.5mg/周）、中剂量（MTX10-12.5mg/周）和高剂量（MTX≥15mg/周）组。在 MTX 治疗的 90 天内，检查天门冬氨酸氨基转移酶（AST）和/或丙氨酸氨基转移酶（ALT）水平升高两倍以上正常值上限（2×ULN）定义的肝毒性。使用逻辑回归分析确定肝毒性的预测因素。
730 例患者中，10 例（1.4%）发生肝毒性。三组 MTX 剂量组之间肝毒性发生率无差异。单因素逻辑回归分析显示，中剂量 MTX 组（比值比（OR）：0.89，95%置信区间（CI）：0.20-4.00，p=0.877）或高剂量 MTX 组（OR：1.23，95%CI：0.24-6.14，p=0.804）肝毒性风险均不高于低剂量 MTX 组。多因素逻辑回归分析显示，基线 AST 和/或 ALT 水平升高超过 ULN 和同时使用来氟米特与 MTX 肝毒性相关。
初始 MTX 剂量与 RA 患者肝毒性增加无关。
•初始甲氨蝶呤（MTX）剂量与类风湿关节炎（RA）患者的肝毒性无关。•基线肝功能检查（LFT）异常或同时接受来氟米特治疗的 RA 患者，在 MTX 治疗早期应密切监测 LFT 异常。
