Sarcoidosis and Methotrexate Toxicity

Methotrexate Toxicity

Liver-function tests might not be all that helpful in determining which patients with sarcoidosis should discontinue tak­ing methotrexate. Researchers from the University of Cincinnati performed 100 liver biopsies in 68 patients with chronic sarcoidosis who had been treated for up to eight years with methotrexate. (To their knowledge, this study represented the largest series of liver-biopsy results in this patient population.)

Toxic drug effects were observed in 14 cases. After examining all the abnormal liver-function test results during the year before the biopsy, however, the researchers found no pattern that might predict toxicity. Patients with hepatic sarcoidosis already had higher levels of various liver enzymes, which meant that the predictive value of the liver-function tests was lost; in addition, more than half of the patients in the methotrexate toxicity group did not have elevated aspartate transami-nase levels in the year before biopsy.
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Methotrexate has become a standard second-line agent for the treatment of sarcoidosis, and hepatotoxicity is a well-known side effect of the drug. Using a liver biopsy to look for a toxic reaction to methotrexate has been controversial, the researchers note, and they point out that rheumatologists have relied on serial liver-function tests to identify at-risk patients with rheumatoid arthritis, based on the relatively low rate of metho-trexate-related liver damage. For patients with sarcoidosis, the policy at the researchers’ institution is to perform a liver biopsy in patients who receive metho-trexate for more than two years.