Changes in methotrexate polyglutamate concentration in patients with rheumatoid arthritis during treatment and after discontinuation (review of two cases)

Abstract

Introduction. The dynamics of changes in the concentration of polyglutamates of methotrexate (MTPG) over the past 20 years has been studied by several scientifc groups using various methods. For a number of reasons, the results of these studies cannot be called uniform and cannot be confdently projected onto the Russian population of patients with rheumatoid arthritis (RA). At the same time, therapeutic drug monitoring of methotrexate (MT) with clearly defned target values of metabolites could be an extremely useful tool in routine clinical practice.Purpose of the study. To characterize the concentration of MTPG in dynamics during treatment and 12 weeks after discontinuation of MT.Materials and methods. Two patients with early RA were traced 4, 12, 24 weeks after MT appointment, and also 12 weeks after its cancellation due to nausea that appeared during treatment. At each visit, an analysis was made for MTPG content by tandem gas chromatography-mass spectrometry.Results. Against the background of treatment, the signifcantly predominant metabolite was MTPG with three and gour residues of glutamic acid (the so-called long-chain), while 12 weeks after discontinuation, MTPG 2 was the predominant fraction.Conclusions. Low values of MTPG 3 and MTPG 4 with high values of MTPG 2 may indicate a recent initiation of treatment or MTB cancellation within the next 3 months. In the event of subjective adverse reactions (ADRs), it is advisable to consider the possibility of switching to a drug analogue of another manufacturer.