Klin Farmakol Farm. 2013;27(3-4):131-135

Pharmacogenetics of methotrexate in treatment of rheumatoid arthritis

Tomáš Veleta¹, Tomáš Soukup², Petr Pávek³, Jana Nekvindová⁴, Jiří Vlček⁵, Petr Bradna²

¹ Oddělení urgentní medicíny Fakultní nemocnice Hradec Králové

² II. interní gastroenterologická klinika Fakultní nemocnice a Lékařské fakulty UK Praha v Hradci Králové

³ Katedra farmakologie a toxikologie Farmaceutické fakulty UK Praha v Hradci Králové

⁴ Ústav klinické biochemie a diagnostiky FN HK a Lékařské fakulty UK Praha v Hradci Králové

⁵ Katedra sociální a klinické farmacie Farmaceutické fakulty UK Praha v Hradci Králové

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 methotrexate treatment. At least one of them occurs in up to 72.9 % of patients, and severe toxicities are identified in up to 30 % of

patients. Pharmacogenetics is a new modern way to enable personalization of clinical drug therapy based on the findings of the genetic

predisposition of 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. Wessels et al found a correlation between polymorphisms

associated with the metabolism of adenosine and a good response to MTX in RA patients, and have proposed a diagnostic predictive

model for RA methotrexate therapy based on genotyping. In 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.

Keywords: rheumatoid arthritis, methotrexate, pharmacogenetics, personalized medicine

Published: December 1, 2013  Show citation