Which Older Patients Most Risk Liver Toxicity From MTX?


A large study of veterans reveals factors that predict which people starting methotrexate for rheumatic diseases after the age of 65 will quickly begin to show signs of liver damage.

Schmajuk G, Miao Y, Yazdany J, et al., Identification of Risk Factors for Elevated Transaminases in Methotrexate Users Through an Electronic Health Record. Arthritis Care & Research (2014) 66:1159–1166 doi: 10.1002/acr.22294.

Older patients new to methotrexate (MTX) may have up to a 90% risk for elevated liver enzymes within a few months of starting the drug if they are obese, have untreated high cholesterol and other comorbid conditions, and don’t take folic acid supplements.

Elevated liver function test results prior to MTX use should be a red flag, according to this retrospective study from the Veterans Health Administration (VHA) system. It involved the records of 659 veterans over age 65 treated for rheumatic diseases, more than half of them for rheumatoid arthritis.

This is the largest population study yet reported assessing risk factors for LFT abnormalities among first-time MTX users.

Researchers at the VA Medical Center and the University of California, San Francisco, utilized the VHA’s national patient databases. They say such automated records could be used to calculate a quick, real-time “MTX hepatotoxicity risk score” before starting the drug.

Abnormal liver function transaminases (LFTs) were considered to be levels above the Upper Limit of Normal (ULN) used at the institution -- 35 mg/ml for aspartate aminotransferase (AST) and 60 mg/ml for alanine aminotransferase (ALT).

To stratify risk, the researchers looked for comorbid conditions, such as:
•  diabetes,
•  poor kidney function,
•  elevated total cholesterol (at or above 240 mg/dL),
•  obesity (body mass index of 30 or above), and
•  use of other drugs with known liver toxicity, such as statins.

The existence of three or more of these predicted the highest risk for moderate ALT and AST elevation (1.5 times the UNL) among new MTX users during the 7-month followup period. This was relatively uncommon, at around 6% of the study group..


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