CHICAGO—Once methotrexate enters a cell through the reduced folate carrier (RFC), which thinks it is picking up folate, the drug is polyglutamated. It is this polyglutamate methotrexate that provides the actual clinical effect. These methotrexate polyglutamate “species” are added and lost over time, but it’s a slow process.
Explore this issueFebruary 2019
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What difference does it make whether a clinician knows this? An understanding of the process makes it more likely a clinician will make sound decisions for their patients, said Joel Kremer, MD, the Pfaff Family Professor of Medicine at Albany Medical College, N.Y., and director of research at The Center for Rheumatology, during the 2018 ACR/ARHP Annual Meeting. He has devoted much of his career to studying methotrexate in patients with rheumatoid arthritis. His back-to-basics talk on the cornerstone drug touched on different modes of methotrexate administration, drug resistance and toxicity.
With methotrexate polyglutamate, the underlying science means rapid dosing escalation is probably not the best approach. “Understanding the complexities of the differential cellular sensitivities to methotrexate can, and should, inform our approach to management,” Dr. Kremer said. “Clinical decisions should be anchored with an understanding of the biochemistry and metabolism of this unique drug.”