Identification of risk factors for elevated transaminases in methotrexate users through an electronic health record

Arthritis Care Res (Hoboken). 2014 Aug;66(8):1159-66. doi: 10.1002/acr.22294.


Objective: To determine the predictors of elevated transaminases in an incident user cohort of older adult patients with rheumatic diseases receiving methotrexate (MTX) using elements derived from an electronic health record.

Methods: Using a national, administrative database of patients seen through the Veterans Health Administration that included pharmacy and laboratory data, we performed an observational cohort study of veterans ages ≥65 years who were new users of MTX to identify risk factors for elevated transaminases.

Results: We studied 659 incident users of MTX. We found a 6% incidence of moderate (≥1.5 × the upper limit of normal) elevations in aspartate aminotransferase or alanine aminotransferase over a mean followup period of 7 months. We identified predictors of moderate transaminase elevations to include obesity (per body mass index ≥30 kg/m(2) ), total cholesterol >240 mg/dl, pre-MTX liver function test (LFT) elevations, use of biologic agents, and lack of folic acid supplementation. A patient with these characteristics and >3 comorbid conditions would be predicted to have a 90% chance of developing a moderate transaminase elevation in the 7 months after starting MTX.

Conclusion: Moderate LFT abnormalities were uncommon in the first 7 months of MTX use, but were more likely to occur in patients with obesity, untreated high cholesterol, pre-MTX LFT elevations, biologic agent use, and lack of folic acid supplementation. Future work should aim to develop a robust, automated prediction rule for identifying patients at high risk for MTX-related liver toxicity.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Chemical and Drug Induced Liver Injury / diagnosis*
  • Cohort Studies
  • Electronic Health Records
  • Female
  • Humans
  • Liver Function Tests
  • Male
  • Methotrexate / adverse effects*
  • Methotrexate / therapeutic use
  • Retrospective Studies
  • Risk Factors
  • Transaminases / blood*


  • Transaminases
  • Methotrexate