scholarly journals AB0263 THE LEVEL OF 7-HYDROXY METHOTREXATE IN BLOOD CELLS IN PATIENTS WITH RHEUMATOID ARTHRITIS DIRECTLY CORRELATES WITH THE LEVEL OF POLYGLUTAMATES OF METHOTREXATE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1158.1-1158
Author(s):  
G. Gridneva ◽  
E. Samarkina ◽  
S. Glukhova ◽  
Y. Muraviev ◽  
A. Kudryavtseva ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Folic Acid ◽  
Blood Cells ◽  
Mononuclear Cells ◽  
Standard Dose ◽  
Drug Efficacy ◽  
Folic Acid Supplementation ◽  
Average Concentration ◽  
Reactive Protein ◽  
Entire Line

Background:7-hydroxy Methotrexate (7-hydroxy-MTX) is a phase I metabolite of MTX, which is converted by hepatic aldehyde oxidases. It is known that 7-hydroxy MTX can reduce the effectiveness of methotrexate, which is associated with increased excretion of methotrexate due to a decrease in polyglutamation and binding to enzymes [1].Objectives:To analyze the level of 7-hydroxy-MTX in peripheral blood cells in order to study the correlation of the level of this metabolite with the level of polyglutamates of methotrexate (MTXPGs).Methods:The prospective study included 65 patients aged 53±11 years, 50 women, 13 men, diagnosed with RA, according to the ACR/EULAR 2020 criteria, methotrexate (MTX) naiive. The duration of the disease was 7,5[4;24] months. All patients were administrated MTX subcutaneously at a dose of 10-15 mg/m2. The visits were carried out at weeks 0, 4, 12, 24 and 36, at all visits samples were taken for the content of MTXPGs with 1,2,3 and 4 glutamate residues and 7-hydroxy MTX separately in red blood cells mass (RBC) and mononuclear cells (MO). The mononuclear fraction was isolated by layering on verografin-ficoll. All patients received folic acid at a standard dose of 5 mg 24 hours after parenteral MTX administration. Samples were collected no earlier than 36 hours after MTX administration. All patients had normal renal function. Disease activity was assessed using the DAS28 index calculated by C-reactive protein.Results:The average concentration of 7-hydroxy MTX is shown in Table 1.Table 1.Level of 7-hydroxy MTX in erythrocytes and mononuclear cells, nmol/L, Median [25; 75 quartiles]7-hydroxy MTX level in:4 weeks12 weeks24 weeks36 weeksRBC18,5[3,1;61,5]10,2[3,6;50,8]10,3[1,7;36,8]7,2[0,1;25,3]MO0,8[0,1;15,2]4,0[0,1;42,2]3,5[0,1;8,1]0,4[0,1;8,9]The level of 7-hydroxy-MTX directly correlated with the level of MTXPGs 1-4, and summary MTXPG in both RBC and MO. Analysis of pairwise correlations according to Pearson showed that: after 4, 12 and 36 weeks, the level of 7-hydroxy-MTX did not correlate with the value of DAS28. After 24 weeks of therapy, the level of 7-hydroxy-MTX in RBC was inversely correlated with DAS28 of the disease (p=0.043).Conclusion:The preliminary results indicate a positive correlation between the level of 7-hydroxy-MTX and MTXPGs in RBC and MO. In this regard, the concentration of 7-hydroxy-MTX can be used as a prognostic marker for MTX therapy in the absence of opportunities in clinical centers to measure the entire line of MTXPGs in RBC and MO. Since the data obtained are somewhat at odds with the few literary sources, it is necessary to conduct further research on this fact.References:[1]Baggott JE, Morgan SL (2009) Methotrexate catabolism to 7-hydroxymethotrexate in rheumatoid arthritis alters drug efficacy and retention and is reduced by folic acid supplementation. Arthritis Rheum 60:2257–2261Disclosure of Interests:None declared

scholarly journals The effect of folic acid supplementation on the toxicity of low-dose methotrexate in patients with rheumatoid arthritis

1990 ◽  
Vol 33 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Sarah L. Morgan ◽  
Joseph E. Baggott ◽  
William H. Vaughn ◽  
Peggy K. Young ◽  
Janet V. Austin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Folic Acid ◽  
Low Dose ◽  
Folic Acid Supplementation ◽  
Acid Supplementation ◽  
Dose Methotrexate

scholarly journals POS0467 STUDY OF METHOTREXATE METABOLITES CONCENTRATIONS IN RED BLOOD CELLS AND MONONUCLEAR CELLS IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 465.2-465
Author(s):  
V. Sygyrta ◽  
G. Gridneva ◽  
A. Lila ◽  
E. Samarkina ◽  
N. Baymeeva ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Red Blood Cells ◽  
Correlation Coefficient ◽  
Blood Cells ◽  
Mononuclear Cells ◽  
Total Concentration ◽  
Pairwise Comparison ◽  
The Body ◽  
Inadequate Response ◽  
Mean Cell Volume

Background: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).Objectives: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 MTPG2, MTPG3 and MTPG4 (MTPG2-4), 7- hydroxymethotrexate (7-OH-MTX) by tandem mass spectrometry.Results:Table 1.Total concentration of MTPG2, MTPG3 and MTPG4 (MTPG2-4), nmol/lMe[25;75]MinMaxWeek 4RBC42.819.0;155.03987.7MO6.25.3;11.91.6147.2Week 12RBC48.117.1;89.00.1519.9MO10.93.9;31.00.9147.6Week 24RBC39.417.2;70.62.7191.8MO8.32.7;14.00.472.4A pairwise comparison of MTX, MTPG2-4 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 MTPG4 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], MTPG2 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], MTPG2 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 MTPG4 level (correlation coefficient 0.51, p <0.05).Conclusion:The inadequate response to MT 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 MTPG4 in mononuclear cells increases more slowly in patients with a longer duration of the disease.Disclosure of Interests:None declared

scholarly journals Therapeutic drug monitoring of methotrexate and its metabolites in the red blood cells and mononuclear cells of patients with rheumatoid arthritis

2020 ◽  
Vol 14 (4) ◽  
pp. 60-64
Author(s):  
G. I. Gridneva ◽  
Yu. V. Muravyev ◽  
N. V. Baimeeva ◽  
V. S. Sygyrta ◽  
S. I. Glukhova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapeutic Drug Monitoring ◽  
Red Blood Cells ◽  
Drug Monitoring ◽  
Blood Cells ◽  
Older Patients ◽  
Time Course ◽  
Mononuclear Cells ◽  
Individual Characteristics ◽  
Therapeutic Drug

Objective: to assess the time course of changes in the concentration of methotrexate (MTX) and its main metabolites in the red blood cells (RBC) and mononuclear cells (MNC) of patients with rheumatoid arthritis (RA), by taking into account individual characteristics (age, statin therapy, and smoking).Patients and methods. The investigation enrolled 33 MTX-treated patients (mean age 53.2±11.7 years) with RA, who underwent therapeutic drug monitoring to measure the RBC and MNC concentrations of free MTX and MTX polyglutamates (MTXPGs) with 2, 3, and 4 glutamate residues (MTXPG 2–4) in using tandem chromatomass spectrometry after 4, 12, and 24 weeks of therapy.Results and discussion. Following 12 weeks, the concentration of MTXPG4 in the MNC was higher in patients taking statins, while that of MTX and MTXPG2 in the RBC were significantly lower than in smokers. At 24 weeks, older patients were observed to have a higher MTX level and a lower MTXPG4 concentration in the RBC.Conclusion. After 24 weeks of therapy, the RBC concentration of MTPG4 was lower and that of MTX was higher in older patients than in others, which confirms data on a slower MTX metabolism in the elderly. The use of statins is likely to have a positive impact on the accumulation of MTXPG. There is a statistically significantly lower RBC concentration of MTXPG in at 12 weeks of therapy.

scholarly journals Real-world experiences of folic acid supplementation (5 versus 30 mg/week) with methotrexate in rheumatoid arthritis patients: a comparison study

Reumatismo ◽  
2016 ◽  
Vol 68 (2) ◽  
pp. 90 ◽  
Author(s):  
K.T. Koh ◽  
C.L. Teh ◽  
C.K. Cheah ◽  
G.R. Ling ◽  
M.C. Yong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cohort Study ◽  
Folic Acid ◽  
Disease Activity Score ◽  
Folic Acid Supplementation ◽  
Observational Cohort Study ◽  
Comparison Study ◽  
Cross Sectional ◽  
Observational Cohort ◽  
Lower Disease Activity

The objective of this study was to compare the tolerability of methotrexate in two different regimes of folic acid (FA) supplementation in rheumatoid arthritis (RA). We performed a multicenter, cross-sectional observational cohort study on 240 RA patients with 120 patients each in 5 mg of FA weekly and 30 mg of FA weekly supplementation. There were no significant differences for side effects (14.2 versus 22.5%, P=0.523) and discontinuation of methotrexate (3.6 versus 13.3%, P=0.085). RA patients given 5 mg of FA weekly supplementation had a lower disease activity score 28 compared to 30 mg of FA weekly supplementation [3.44 (1.10) versus 3.85 (1.40), P=0.014]. FA supplementation of 5 mg per week and 30 mg per week was associated with similar tolerability of methotrexate in RA patients.

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