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Fostamatinib + methotrexate is a combination therapy used primarily in clinical research and trials for rheumatoid arthritis, especially in patients with an inadequate response to methotrexate alone. Fostamatinib is an oral small molecule prodrug that is rapidly converted to its active metabolite, R406, which inhibits spleen tyrosine kinase (Syk), a key enzyme involved in immune cell signaling pathways that drive inflammation and joint destruction. Methotrexate is a folate analog antimetabolite that inhibits enzymes involved in nucleotide synthesis, leading to anti-inflammatory effects and immunosuppression. The combination has been shown to provide additive or modestly improved efficacy over either agent alone in reducing disease activity and joint damage in rheumatoid arthritis models and clinical studies[1][2][4][5]. Fostamatinib was developed by Rigel Pharmaceuticals; AstraZeneca has also been involved as a development partner[2][5]. Methotrexate is widely manufactured as a generic drug.
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