Human CD14+ monocytes from early inflammatory arthritis patients before and after a 5day-and 30day-period of methotrexate treatment

Methotrexate (MTX) continues to be the anchor drug for patients with rheumatoid arthritis and psoriatic arthritis (RA and PsA) both as monotherapy as well as in combination with other drugs because of its efficacy, safety, low relative cost and the possibility of individualizing dose and method of administration. Following low-dose administration, MTX typically reaches peak plasma concentrations after 1-2 h, and almost completely disappears from the circulation by 24 h. Cellular uptake of MTX is mediated by the Reduced Folate Carrier. Once internalize, MTX is converted into MTX-polyglutamates (MTX-PG), a process that is catalyzed by folylpolyglutamate synthase (FPGS), which sequentially adds glutamic acid residues to MTX, and is one of the critical factors for the therapeutic action of MTX. We carried out a clinical observational study to evaluate the influence of MTX-PG levels on the molecular inflammatory state of monocytes from arthritis patients and relate to the clinical efficacy of MTX.