Utility of the methotrexate test dose

Does methotrexate require a test dose?

This question was investigated by researchers led by Dr. Morgan Wilson from Southern Illinois University School of Medicine, Springfield, IL. The guidelines suggest that providing a small test dose of methotrexate to patients followed by laboratory evaluation can minimize the risk of serious adverse events associated with methotrexate.

Methotrexate competitively inhibits DHFR. This leads to decreased synthesis of DNA, RNA, thymidylates, and proteins. Methotrexate can cause stomatitis, cytopenias, and rarely hepatotoxicity with cirrhosis. Several clinical trials using methotrexate without a test dose reported very low serious adverse reactions. This led the researchers to question the utility of a test dose in dermatologic conditions.

The researchers performed a retrospective study comparing patients who received methotrexate with a test dose and patients who received methotrexate without a test dose. The electronic medical record was used to retrieve patient records over the course of five years (2010-2015). All patients who were prescribed methotrexate were selected.

Test dose was defined as initial methotrexate dose of less than or equal to 10 mg with laboratory monitoring prior to the second weekly dose. The initial research identified 812 patients with 174 patients included in the analysis. Interestingly, most dermatology patients received a test dose while most rheumatology patients did not.

The patients that received the test dose had significantly more lab draws than their comparators during the first four months of therapy. In both groups, there were no deaths or hospitalizations associated with methotrexate toxicity. Labs obtained one week after test dosing showed no serious lab abnormalities and prompted one management change due to grade 1 ALT elevation of uncertain etiology. There were no discontinuations due to hematologic toxicity in either group.

Early in the course of methotrexate therapy, discontinuations were usually secondary to nausea or other gastrointestinal symptoms as opposed to toxicity. The study found very little benefit to test dosing in patients receiving low dose methotrexate. The study is limited by its retrospective design and the small number of participants. Also, elderly patients, as well as patients with known renal disease or liver disease, may benefit from test dosing.

References:

Herrmann, Thomas, Michael Buhnerkempe, and Morgan L. Wilson. "Initiation of methotrexate with or without a test dose: a retrospective toxicity study." Journal of the American Academy of Dermatology (2018).