Low-dose methotrexate is the cornerstone disease-modifying anti-rheumatic drug in the treatment of patients with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). Although MTX levels can be measured easily in plasma, low-dose MTX is rapidly cleared from plasma and is therefore not routinely measured. In contrast, MTX is transported into and retained in cells long after it has been eliminated from plasma. We have developed an LC-MS/MS assay to measure MTX-polyglutamates (MTX-PG) in erythrocytes and measured drug concentrations in three prospective cohort studies in RA and JIA patients. Erythrocyte MTX-PG levels were related to clinical response in all cohorts and hence, could be used for therapeutic drug monitoring of low-dose MTX therapy. Moreover, higher baseline erythrocyte folate was associated with higher erythrocyte MTX-PG accumulation and improved clinical response. Determinants of MTX-PG concentrations were age, polymorphisms in ABC transporters, erythrocyte folate and dosing.
Disclosure of Interest None declared