leflunomide + methotrexate

Leflunomide + methotrexate is a combination of two conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) used primarily for the treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Leflunomide inhibits dihydroorotate dehydrogenase, thereby blocking pyrimidine synthesis and reducing lymphocyte proliferation. Methotrexate acts as an anti-metabolite by inhibiting dihydrofolate reductase, interfering with purine and pyrimidine metabolism, which suppresses immune cell activity. The combination is typically considered in patients who have inadequate response to monotherapy with either agent. Clinical studies show that this combination can provide significant improvement in disease activity compared to monotherapy, though it requires careful monitoring due to increased risk of hepatotoxicity and other adverse effects[1][2][3][4][5][6].