Abstract
Methotrexate is one of the essential medicines used in the treatment of rheumatoid arthritis (RA). The efficacy of treatment of rheumatoid arthritis with methotrexate (MTX) is between 46 % and 65 % (as assessed by ACR 20).
A number of undesirable effects are associated with At least one of them occurs in up to 72.9 % of patients, and severe toxicities are identified in up to 30 % of patients. the patient to respond to the treatment. Research into MTX pharmacogenetics in rheumatoid arthritis focuses on the relationship between the therapeutic effect and toxicity of MTX, mutations in the genes of metabolic pathways, MTX transporters, and genes involved in the effect of adenosine, HLA-G antigens and enzymes of the metabolism of nucleic acids.
One of the most widely studied genes is the one encoding the enzyme 5,10-methylenetetrahydrofolate reductase, whose mutation is probably related to an extension of adverse gastrointestinal effects of MTX. There have been promising results from studies examining polymorphisms associated with the metabolism of adenosine.
There was a significant correlation between some of these polymorphisms and the clinical effect of MTX, according to both DAS28 score and the occurrence of adverse effects of MTX. n summary, the results of the studies suggest a possible diagnostic value for genotyping of patients with RA for prediction of MTX therapy and their ability to tolerate higher doses of MTX therapy, or conversely to determine patients primarily resistant to the therapy by reason of a predisposition to serious side effects. In the future, it will be necessary to analyze the available results in studies with larger numbers of patients and longer follow-up.