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Abstract
Methotrexate (MTX), 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 MTX therapy in RA; that is, the field of MTX pharmacogenetics. This review will summarize key pharmacogenetic studies examining SNPs in the genes encoding enzymes in the MTX cellular pathway and their association with MTX response in RA. As evident from this review, MTX pharmacogenetics in RA remains a muddled field, mostly due to inconsistent results from several small underpowered studies.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.