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Key Points Methotrexate shows good efficacy in a proportion of patients: 40% of treated patients with rheumatoid arthritis achieve an ACR50 response The mechanism of action of methotrexate has not fully been defined, however potentiation of adenosine signalling carries the most robust data Pharmacokinetic parameters, particularly intracellular methotrexate polyglutamation, show some association with disease activity, although they cannot yet be used to predict treatment response An exploration of the expression and polymorphisms of genes encoding molecules linked to proposed mechanisms of methotrexate action is underway to identify methotrexate-responsive signatures At present, no robust markers or predictive models exist for methotrexate responsiveness in RA Abstract The treatment and outcomes of patients with rheumatoid arthritis (RA) have been transformed over the past two decades

Glutathione regulates susceptibility to oxidant-induced mitochondrial DNA damage in human lymphocytes

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NS: Funding acquisition, Project administration, Resources, Supervision, Visualization, Writing original draft, Writing review & editing

18 Further comments on this RCT are available in the Limitations section