Methotrexate pharmacogenetics in rheumatoid arthritis: a status report

Methotrexate (MIX), an antifolate drug, is the first-line disease-modifying agent for the treatment of rheumatoid arthritis (RA) worldwide. MTX has excellent long-term efficacy, tolerability and safety. Early initiation of MTX in patients with RA controls joint destruction and slows progression of disease. However, the clinical response to MTX and frequency of adverse effects from the drug exhibit marked interpatient variability. Over the past decade, there has been a quest to identify genetic markers that reliably predict MTX efficacy and toxicity and help optimize MIX therapy in RA; that is, the field of MIX pharmacogenetics. This review will summarize key pharmacogenetic studies examining SNPs in the genes encoding enzymes in the MIX cellular pathway and their association with MIX response in RA. As evident from this review, MIX pharmacogenetics in RA remains a muddled field, mostly due to inconsistent results from several small underpowered studies.