Methotrexate and leflunomide are two cornerstone medications commonly used in the treatment of autoimmune diseases, particularly rheumatoid arthritis and psoriatic arthritis. Both drugs have proven effective in managing symptoms and slowing disease progression. However, they work through different mechanisms and have distinct side effect profiles, which can influence a physician’s choice depending on the patient’s specific condition and medical history. Methotrexate, initially developed as an anti-cancer drug, has established itself as a first-line treatment for various inflammatory and autoimmune conditions. It is an antimetabolite that interferes with DNA synthesis, thereby reducing the proliferation of rapidly dividing cells, including those involved in the immune response. On the other hand, leflunomide is…