Article
Concentrations of methotrexate metabolites in red blood cells and mononuclear cells in rheumatoid arthritis
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Authors
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Galina Gridneva
- V.A. Nasonova Rheumatology Research Institute
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Eugenia Aronova
- V.A. Nasonova Rheumatology Research Institute
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Anastasia Kudryavtseva
- V.A. Nasonova Rheumatology Research Institute
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Svetlana Glukhova
- V.A. Nasonova Rheumatology Research Institute
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Elena Samarkina
- V.A. Nasonova Rheumatology Research Institute
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Yury Muraviev
- V.A. Nasonova Rheumatology Research Institute
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Natalia Baymeeva
- Mental Health Centre
| Published: | September 14, 2021 |
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Outline
Text
Introduction: Studying the dynamics of the methotrexate metabolites concentration in cells will help to predict the therapeutic effect and assess patient compliance. We suggest that studying the dynamics of changes in the concentration of methotrexate metabolites in mononuclear cells (MO) may be a more accurate method than measuring in red blood cells (RBC). The aim of the research is to study the dynamics of changes in the concentration of MTX and its metabolites in RBC and MO in methotrexate-naive patients with RA.
Methods: 33 patients (26 women, 7 men) aged 53.2 ± 11.7 years with a diagnosis of rheumatoid arthritis, according to the ACR/EULAR 2010 criteria, were included. All patients had GFR >60 ml/min. Patients were monitored after 4, 12, 24 and 36 weeks from the start of МТX. Mean Cell Volume (MCV) of RBC was measured by standard methods. Samples of RBC and MO were collected separately to determine the concentrations of MTX (basic monoglutamate form), total concentration of MTXPG with 2, 3 or 4 glutamate residues (MTPG2, MTPG3 and MTXPG4), 7- hydroxymethotrexate (7-OH-MTX) by tandem mass spectrometry.
Results: A pairwise comparison of MTX, MTXPG2-4 and 7-OH-MTX concentrations, according to the Wilcoxon method did not reveal statistically significant differences at weeks 4,12 and 24. The concentration of the studied substances did not correlate with the value of the body mass index, taking statins, glucocorticoids, a cumulative dose of MTX, and the frequency of adverse reactions. At the week 4, of therapy, the level of MTXPG4 in MO was inversely correlated with the duration of the disease (correlation coefficient - 0.58, p 0.05) The concentration of MTX and its metabolites in MO was lower in smokers (MTX 11.2 [2.6;21.9], 7-OH-MTX 2.1 [0.5; 10.4], MTXPG2 0.5 [0.1;1.3]) than in non-smokers (MTX 46.5 [25.3;97.5], 7-OH-MTX 28.2 [7.1; 64.7], MTXPG2 8.2 [4.1;32.9]), p = 0.02, 0.01 and 0.003, respectively. At week 24 of therapy, a negative correlation was found between age and MTXPG4 level (correlation coefficient 0.51, p <0.05).
Conclusion: The inadequate response to MTX therapy in smokers, described in many previous studies, may be associated with a low concentration of the MTX metabolites in mononuclear cells. The level of MTXPG4 in mononuclear cells increases more slowly in patients with a longer duration of the disease.
Disclosures: None declared
