Leflunomide's mechanism of action is best described as which of the following?

• A. Prodrug that inhibits pyrimidine synthesis
• B. Inhibits TNF
• C. Inhibits COX-2
• D. Stimulates T cells

Answer: (B)

Leflunomide works by hindering the production of pyrimidines, which are essential for DNA synthesis in rapidly dividing cells like activated T and B lymphocytes. It is a prodrug that is converted to its active metabolite, teriflunomide, which inhibits dihydroorotate dehydrogenase (DHODH), blocking de novo pyrimidine synthesis. Because proliferating lymphocytes rely on this pathway, Leflunomide effectively reduces their expansion and dampens immune responses. It does not block TNF signaling, it’s not a COX-2 inhibitor, and it does not stimulate T cells. Therefore, describing Leflunomide as a prodrug that inhibits pyrimidine synthesis best captures its mechanism.