Figure 1

Summary of mechanism of action of widely used small molecule DMARDs. MTX is a folic acid antagonist (acts by inhibiting dihydro-folate reductase, DHFR). Leflunomide inhibits pyrimidine synthesis in T lymphocytes (acts by inhibiting dihydroorotate dehydrogenase, DOD). Sulfasalazine exerts immune-suppressive effect by pooling adenosine. All three drugs inhibit activation of T cell and antigen presenting cells (APC), and consequent augmented release of pro-inflammatory interleukins and TNF. By these mechanisms, these DMARDs suppress activation of target cells in the joint and mitigate progression of RA.