Pharmacogenetics of methotrexate in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic inflammatory disorder that mainly affects the joints. Despite the availability of the new biological agents such as TNF-blocking agents, methotrexate (MTX) remains as the primary agent for the treatment of RA due to the low and broad experience with its use. The efficacy and adverse drug reactions of MTX are variable among patients, and this is partially contributed in genetic difference of drug-metabolizing enzymes, transporters, and receptors In this review, we described MTX pharmacogenetics that was related to a large interindividual variation on efficacy and adverse drug reactions in RA patients, including MTX transporter pharmacogenetics, MTX glutamation pharmacogenetics, folate pathway pharmacogenetics, and adenosine pathway pharmacogenetics. We also described the clinical implications between their pharmacogenetics and clinical outcomes (efficacy and/ or adverse drug reactions of MTX).