Pharmacogenomics of Methotrexate in Diverse Populations

Methotrexate (MTX) is a commonly used disease modifying antirheumatic drug (DMARD) for the treatment of RA because of its affordability, long-term efficacy and acceptable toxicity profile. MTX isalso frequently used in the treatment of other forms of inflammatory arthritis. Although MTX is considered to be a well-tolerated DMARD, there is a significant inter-patient variability in the toxicity and efficacy of MTX treatment. MTX treatment response is often multi-factorial, resulting from complex interplay of various factors such as age, sex, ethnicity, disease duration, disease severity and activity, presence of Creactive protein and RF factor. 

It is also clear that genetic factors also make an important contribution to treatment variability.Folate metabolism is the keytherapeutic target of MTX, and numerous studies support the idea that genetic variations in genes encoding Folate-MTX transporters and metabolizing enzymes may impact MTX therapeutic outcome by affecting efficiency of these enzymes.