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This is a combination of six immunomodulatory drugs, five of which are tumor necrosis factor alpha (TNF-alpha) inhibitors—certolizumab pegol, etanercept, adalimumab, infliximab, and golimumab—and one conventional disease-modifying antirheumatic drug (DMARD), methotrexate. All five TNF inhibitors are monoclonal antibodies or fusion proteins that bind to and neutralize TNF-alpha, a cytokine involved in systemic inflammation. Methotrexate is a small molecule antimetabolite that inhibits dihydrofolate reductase and other enzymes involved in nucleotide synthesis and immune cell proliferation. These agents are primarily used for the treatment of autoimmune diseases such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, plaque psoriasis, and other inflammatory conditions. The concurrent use of multiple biologic DMARDs or combining biologics with methotrexate increases immunosuppressive effects but also significantly raises the risk of serious infections; therefore such combinations are generally not recommended in clinical practice[2][9].
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