Se Rim Choi1, Jun Won Park1, Eun Bong Lee1, Jin Kyun Park2. 1. 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. 2. 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. jinkyunpark@gmail.com.
Abstract
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.
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.
Authors: L Idolazzi; S Adami; R Capozza; G Bianchi; A Cozzolongo; O Epis; E Fusaro; G Lapadula; A Migliore; R Pellerito; A Pucino; L Sinigaglia; Elisa Visalli; Maurizio Rossini Journal: Clin Exp Rheumatol Date: 2015-12-15 Impact factor: 4.473