adalimumab + etanercept + methotrexate

This is a combination therapy consisting of three agents used in the management of autoimmune and inflammatory diseases, particularly rheumatoid arthritis. - **Adalimumab** is a monoclonal antibody that targets and neutralizes tumor necrosis factor-alpha (TNF-α), a cytokine involved in systemic inflammation. - **Etanercept** is a fusion protein that acts as a decoy receptor for TNF-α, thereby inhibiting its activity. - **Methotrexate** is a conventional disease-modifying antirheumatic drug (DMARD) that inhibits dihydrofolate reductase, interfering with DNA synthesis and exerting anti-inflammatory effects through increased adenosine signaling and other immunoregulatory pathways. While each agent can be used alone or in dual combinations (adalimumab + methotrexate or etanercept + methotrexate), the triple combination of adalimumab, etanercept, and methotrexate together is not standard clinical practice due to overlapping mechanisms (both biologics target TNF-α) and increased risk of adverse effects without proven additional benefit over dual therapy[1][6][7]. The rationale for combining these drugs would be to maximize suppression of inflammation in refractory cases; however, guidelines generally recommend against using two biologic TNF inhibitors concurrently due to safety concerns.