Related Experiment Video
Updated: Nov 2, 2025
Preliminary Study on Acupuncture Combined with Grain-sized Moxibustion for Treating Rheumatoid Arthritis with Finger Joint Pain
Published on: May 16, 2025
Initial methotrexate dosage is not associated with an increased risk of liver toxicity in patients with rheumatoid
Se Rim Choi1, Jun Won Park1, Eun Bong Lee1
1Division 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.
Objective:
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).
Methods:
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.
Results:
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.
Conclusion:
The initial MTX dosage is not associated with increased hepatotoxicity in RA patients.
Key Points:
• 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.
Insights
Initial methotrexate (MTX) dosage does not increase liver toxicity risk in rheumatoid arthritis (RA) patients. Monitor RA patients with baseline liver abnormalities or on leflunomide closely for liver function during early MTX treatment.
Area of Science:
- Rheumatology
- Hepatology
- Pharmacology
Background:
- Rheumatoid arthritis (RA) is a chronic autoimmune disease.
- Methotrexate (MTX) is a common disease-modifying antirheumatic drug (DMARD) used for RA.
- Liver toxicity is a potential concern with MTX therapy.
Purpose of the Study:
- To investigate the association between initial MTX dosage and the risk of liver toxicity in RA patients.
- To identify predictors of MTX-induced hepatotoxicity.
Main Methods:
- Retrospective study of 730 RA patients initiating MTX.
- Patients categorized into low, intermediate, and high initial MTX dosage groups.
- Hepatotoxicity defined as AST/ALT elevation >2x ULN within 90 days of MTX treatment.
- Logistic regression analysis to identify predictors of hepatotoxicity.
Main Results:
- Hepatotoxicity occurred in 1.4% of patients.
- No significant difference in hepatotoxicity rates across MTX dosage groups.
- Elevated baseline AST/ALT and concurrent leflunomide use were associated with MTX hepatotoxicity.
Conclusions:
- Initial MTX dosage is not a significant risk factor for liver toxicity in RA patients.
- Baseline liver function and concomitant leflunomide use warrant close monitoring during early MTX treatment.
Related Concept Videos
01:29Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
01:29Therapeutic Drug Monitoring: Affecting Factors
01:08Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment
01:24Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
01:21Rheumatic Heart Disease III: Medical Management
01:22Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test