sulfasalazine + methotrexate + leflunomide

This is a combination therapy consisting of three conventional synthetic disease-modifying antirheumatic drugs (csDMARDs): sulfasalazine, methotrexate, and leflunomide. All three agents are used in the management of rheumatoid arthritis (RA) and other autoimmune diseases. Methotrexate acts as an antifolate agent inhibiting dihydrofolate reductase, thereby suppressing DNA synthesis and immune cell proliferation. Sulfasalazine is believed to modulate inflammatory mediators and inhibit prostaglandin synthesis, though its precise mechanism in RA remains unclear. Leflunomide is a prodrug whose active metabolite inhibits dihydroorotate dehydrogenase, blocking de novo pyrimidine synthesis required for lymphocyte proliferation[6][7][8]. The combination aims to enhance efficacy by targeting multiple pathways involved in inflammation and autoimmunity but requires careful monitoring due to increased risk of adverse effects such as hepatotoxicity[1][2].