azathioprine + methotrexate

Azathioprine + methotrexate is a combination of two immunosuppressive small molecule drugs, both classified as disease-modifying antirheumatic drugs (DMARDs). This combination is used primarily in the management of autoimmune diseases such as rheumatoid arthritis and has also been studied for use in atopic dermatitis and psoriasis. Azathioprine acts mainly by inhibiting purine synthesis, leading to suppression of B and T lymphocyte proliferation. Methotrexate inhibits dihydrofolate reductase, blocking folate metabolism and DNA synthesis, but its anti-inflammatory effect in rheumatology is largely attributed to increased adenosine signaling, which suppresses inflammation. The combination may offer synergistic immunosuppression due to their complementary mechanisms; however, studies show that while efficacy may be similar or slightly improved compared to monotherapy with methotrexate alone, there can be an increased risk of adverse effects requiring careful monitoring[1][2][3][4][5][6].