Polymorphisms for the Clinical Efficacy and Toxicity of Methotrexate in Patients with Rheumatoid Arthritis: Systemic Review

Ahlam Alharthi, Rania Magadmi and Maha Jamal

Methotrexate is a medication known as an antimetabolite and acts as an anti-folate. Methotrexate has proven to be an efficient, quick-acting DMARD and its widespread use in the management of rheumatoid arthritis. The main genetic variations in proteins that affect the kinetics and efficiency profile of methotrexate are described in this review’s objectives. A literature review was conducted from January, 2013 to March, 2023 using the PubMed and Embase bibliographic databases. The search was focusing on methotrexate, pharmacogenetics, pharmacokinetics and rheumatoid arthritis. The research criteria were met by 133 articles in total, which were then analyzed. Increased activity of ABC transporters can lead to lower MTX concentrations in cells and reduced therapeutic response. The SLCO1B1 gene variant 521 C/T is associated with better MTX response and lower risk of MTX toxicity. The TYMS gene’s 3R allele genotype is linked to reduced efficacy and increased toxicity. Methotrexate indirectly inhibits the MTHFR enzyme and the MTHFR gene variants C677T and A1298C are associated with diminished effectiveness and increased toxicity of MTX. Several gene variants influence MTX response; however, the individual effects of each variant are probably not significant. This demonstrates the increasing demand for better gene characterization and a deeper comprehension of variant distribution by ethnicity.

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