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Mechanism of action of methotrexate in rheumatoid arthritis, and the search for biomarkers

Lookup NU author(s): Dr Philip Brown, Dr Arthur PrattORCiD, Professor John IsaacsORCiD


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The treatment and outcomes of patients with rheumatoid arthritis ( RA) have been transformed over the past two decades. Low disease activity and remission are now frequently achieved, and this success is largely the result of the evolution of treatment paradigms and the introduction of new therapeutic agents. Despite the rapid pace of change, the most commonly used drug in RA remains methotrexate, which is considered the anchor drug for this condition. In this Review, we describe the known pharmacokinetic properties and putative mechanisms of action of methotrexate. Consideration of the pharmacodynamic perspective could inform the development of biomarkers of responsiveness to methotrexate, enabling therapy to be targeted to specific groups of patients. Such biomarkers could revolutionize the management of RA.

Publication metadata

Author(s): Brown PM, Pratt AG, Isaacs JD

Publication type: Review

Publication status: Published

Journal: Nature Reviews Rheumatology

Year: 2016

Volume: 12

Issue: 12

Pages: 731-742

Print publication date: 01/12/2016

Online publication date: 27/10/2016

Acceptance date: 01/01/1900

ISSN (print): 1759-4790

ISSN (electronic): 1759-4804



DOI: 10.1038/nrrheum.2016.175