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Review
. 2016 Dec;12(12):731-742.
doi: 10.1038/nrrheum.2016.175. Epub 2016 Oct 27.

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

Philip M Brown  1 , Arthur G Pratt  1 , John D Isaacs  1
Affiliations
Review

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

Philip M Brown et al. Nat Rev Rheumatol. 2016 Dec.

Abstract

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.

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