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

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/m²), 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.