Methotrexate pharmacogenetics in rheumatoid arthritis: A status report

Fardina Malik, Prabha Ranganathan

Research output: Contribution to journalReview articlepeer-review

49 Scopus citations


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.

Original languageEnglish
Pages (from-to)305-314
Number of pages10
Issue number3
StatePublished - Feb 2013


  • arthritis
  • methotrexate
  • pharmacogenetics
  • polymorphism
  • rheumatoid


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