title: Mechanism of action of methotrexate in rheumatoid arthritis, and the search for biomarkers.
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.
authors: Institute of Cellular Medicine, Faculty of Medical Sciences, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
authors: Philip M
authors: PM
authors: Brown
authors: Institute of Cellular Medicine, Faculty of Medical Sciences, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
authors: Arthur G
authors: AG
authors: Pratt
authors: Institute of Cellular Medicine, Faculty of Medical Sciences, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
authors: John D
authors: JD
authors: Isaacs
mesh_terms: D000241:Adenosine / Q000378:metabolism; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D015415:Biomarkers; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism; D005493:Folic Acid Antagonists / Q000494:pharmacology; D006801:Humans; D045726:Metalloproteases / Q000187:drug effects / Q000378:metabolism; D008727:Methotrexate / Q000494:pharmacology* / Q000627:therapeutic use; D008745:Methylation / Q000187:drug effects; D000071184:Pharmacogenomic Variants / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D016207:Cytokines; D015777:Eicosanoids; D005493:Folic Acid Antagonists; D017382:Reactive Oxygen Species; D045726:Metalloproteases; D000241:Adenosine; D008727:Methotrexate