Optimising low-dose methotrexate for rheumatoid arthritis-A review

Br J Clin Pharmacol. 2019 Oct;85(10):2228-2234. doi: 10.1111/bcp.14057. Epub 2019 Aug 9.


Methotrexate at low doses (5-25 mg/week) is first-line therapy for rheumatoid arthritis. However, there is inter- and intrapatient variability in response, with contribution of variability in concentrations of active polyglutamate metabolites, associated with clinical efficacy and toxicity. Prescribing remains heterogeneous across population groups, disease states and regimens. This review examines current knowledge of dose-response of oral methotrexate in the setting of rheumatoid arthritis, and how this could help inform dosage regimens.

Keywords: clinical pharmacology; methotrexate; pharmacodynamics; pharmacokinetics; prescribing; rheumatoid arthritis.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Antirheumatic Agents / administration & dosage*
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / pharmacokinetics
  • Arthritis, Rheumatoid / drug therapy*
  • Dose-Response Relationship, Drug
  • Humans
  • Methotrexate / administration & dosage*
  • Methotrexate / adverse effects
  • Methotrexate / pharmacokinetics
  • Polyglutamic Acid / metabolism
  • Practice Patterns, Physicians'


  • Antirheumatic Agents
  • Polyglutamic Acid
  • Methotrexate