scholarly journals Methotrexate catabolism to 7-hydroxymethotrexate in rheumatoid arthritis alters drug efficacy and retention and is reduced by folic acid supplementation

2009 ◽  
Vol 60 (8) ◽  
pp. 2257-2261 ◽  
Author(s):  
Joseph E. Baggott ◽  
Sarah L. Morgan
Keyword(s):  
Rheumatoid Arthritis ◽  
Folic Acid ◽  
Drug Efficacy ◽  
Folic Acid Supplementation ◽  
Acid Supplementation

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 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 Effect of Folic Acid Supplementation for Reducing Methotrexate Side Effects in Patients with Rheumatoid Arthritis: an Evidence-based Case Report

2021 ◽  
Vol 12 (2) ◽  
pp. 274-278
Author(s):  
Athira Presialia ◽  
Bambang Setyohadi
Keyword(s):  
Rheumatoid Arthritis ◽  
Folic Acid ◽  
Side Effects ◽  
Liver Toxicity ◽  
Statistical Significance ◽  
Signs And Symptoms ◽  
Folic Acid Supplementation ◽  
Joint Disease ◽  
Acid Supplementation ◽  
Gastrointestinal Side Effects

Background: Rheumatoid arthritis is a chronic inflammatory joint disease,indicated by a symmetrical erosive synovitis. Disease-modifying anti-rheumaticdrugs (DMARDs) are known to interfere with signs and symptoms of RA, improvephysical function and therefore increase patient productivity. Methotrexate is ananchor drug for rheumatoid arthritis patients, however, its related mechanism ofaction with folate deficiency resulting in some side effects, includinggastrointestinal and liver toxicity. Folic acid supplementation may reduce theseside effects. Method: A search was conducted on Pubmed, Cochrane, EBSCOhost,and ProQuest. After the selection of title and abstract was done using inclusionand exclusion criteria, which led to one relevant article. The selected study wascritically appraised for its validity, importance, and applicability. Result: Inrheumatoid arthritis patient receiving methotrexate, there was a statisticallysignificant reduction in the incidence of abnormal transaminase elevation (RR:0.19, 95% CI: 0.10-0.36), but the reduction in gastrointestinal side effects did notreach statistical significance (RR: 0.76, 95% CI: 0.57-1.01) Conclusion: Folic acidsupplementation has an effect in reducing gastrointestinal and liver toxicity as sideeffects of methotrexate in rheumatoid arthritis patients.

Usefulness of daily folic acid supplementation during methotrexate treatment of Japanese patients with rheumatoid arthritis

2020 ◽  
Vol 31 (1) ◽  
pp. 108-113
Author(s):  
Keiichi Sasaki ◽  
Toshikazu Tsuji ◽  
Yasutaka Kimoto ◽  
Yuki Yanagihara ◽  
Ken Masuguchi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Folic Acid ◽  
Japanese Patients ◽  
Folic Acid Supplementation ◽  
Acid Supplementation ◽  
Methotrexate Treatment
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