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Initial methotrexate dosage is not associated with an increased risk of liver toxicity in patients with rheumatoid arthritis

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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.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

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Funding

This study was in part supported by the generous donation by Soon Yeon Kim and Wang Kyum Kim to support research in rheumatic diseases.

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Authors and Affiliations

  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

    Se Rim Choi, Jun Won Park, Eun Bong Lee & Jin Kyun Park

Authors
  1. Se Rim Choi
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  2. Jun Won Park
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  3. Eun Bong Lee
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  4. Jin Kyun Park
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Contributions

Research conception and design, Eun Bong Lee, Jin Kyun Park; Data acquisition, Se Rim Choi; Data analyses and interpretation, Se Rim Choi, Jun Won Park; Statistical analyses, Se Rim Choi, Jun Won Park; Drafting manuscript, Se Rim Choi; Critical revision of the manuscript, Jun Won Park, Eun Bong Lee, Jin Kyun Park. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Jin Kyun Park.

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Ethics approval and consent to participate

The study was approved by the Institutional Review Board of the Seoul National University Hospital (IRB No. 1904–009-1023). The study was performed in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Patient consent was waived by the IRB.

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Not applicable.

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None.

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Choi, S.R., Park, J.W., Lee, E.B. et al. Initial methotrexate dosage is not associated with an increased risk of liver toxicity in patients with rheumatoid arthritis. Clin Rheumatol 40, 4493–4500 (2021). https://doi.org/10.1007/s10067-021-05811-7

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  • DOI: https://doi.org/10.1007/s10067-021-05811-7

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