A goal of RA therapy is to regulate autoimmune lymphocytes, while sparing other lymphocytes that provide protection against exogenous infectious agents and other cell types in the body. Leflunomide provides anti-rheumatic activity at doses that are not associated with leukopenia, thrombocytopenia, or severe mucositis.
The mechanism of action of leflunomide is not fully understood. It is proposed that leflunomide (after conversion intoits active metabolite) exerts its immunomodulatory activity by inhibition of de novo ribonucleotide synthesis at the level of the enzyme dihydroorotate dehydrogenase (DHODH) and subsequent lowering rUMP levels. This inhibition will lead to translocation of p53 to the nucleus and activation of a series of steps that block cell cycle progression.
It takes 4-8 weeks before onset of effect. In clinical trials, leflunomide has been associated with liver transaminase elevations 3 times the upper limit of normal. Routine monitoring should include complete blood count and hepatic panel every 2 weeks for the first month and then on a monthly basis. Other adverse effects of leflunomide are hypertension, diarrhea, GI upset and alopecia.