Personalization of Treatment with Methotrexate in Rheumatoid Arthritis Patients

Personalized therapy is the ability to classify individuals into subpopulations that differ in their susceptibility to a particular disease or their response to a specific treatment. Methotrexate is antimetabolite approved for management of rheumatoid arithritis (RA). Personalization of treatment with methotrexate in RA patients has been studied. The most common non-synonymous variants studied were the C677T (Ala222Val) and A1298C (Glu429Ala). They were described for the Methylenetetrahydrofolate reductase gene and associated with a decreased enzymatic activity and an alteration of intracellular folate distribution. Identification and validation of polygenic determinants is essential to translate these discovered pharmacogenetic markers into widespread clinical practice with development of pre-treatment standardised genetic tests and molecular diagnostic commercial kits. Such diagnostic tools would lead to a better management of RA, might minimizing patient exposure to unnecessary medications and toxicities. Further studies addressing these key points are essential.