MTX is a folate analogue drug used in low dose for the treatment of rheumatoid arthritis, severe psoriasis, and inflammatory bowel disease (IBD). The effects of MTX are depletion of reduced folates through inhibition of dihydrofolate reductase (DHFR). Once MTX enters the cell, it is polyglutamated with up to seven glutamate residues through the action of folylpolyglutamyl synthetase (FPGS). Polyglutamates 2-7 are stored intracellularly inhibiting different enzymes. Monitoring Methotrexate polyglutames in red blood cells is useful for confirming adherence to therapy.
For psoriasis and IBD patients, monitoring MTX and PLG2-5 levels is useful for confirming adherence to methotrexate therapy. For RA, recent studies have suggested that there is a correlation between levels of MTXGlu 3-5 and disease activity. Patients with total MTXGlu3-5 levels <60nM are more likely to have poor clinical response.