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Full efficacy requires 1-2 weeks, likely due to adaptive changes in receptor density

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Mechanisms proposed to explain the effects of MTX in RA include antagonism of folate-dependent processes, stimulation of adenosine signaling, inhibition of methyl-donor production, generation of reactive oxygen species, downregulation of adhesion-molecule expression, modification of cytokine profiles, and downregulation of eicosanoids and matrix metalloproteinases [9]