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Guselkumab (CNTO 1959) is a fully human immunoglobulin G1 lambda monoclonal antibody that targets the p19 subunit of interleukin-23 (IL-23), blocking its interaction with the IL-23 receptor and inhibiting downstream signaling and cytokine production. This mechanism reduces inflammation associated with autoimmune diseases. Guselkumab is primarily indicated for plaque psoriasis and psoriatic arthritis and has also been studied in ulcerative colitis. Methotrexate is a small molecule antimetabolite that inhibits dihydrofolate reductase (DHFR), interfering with DNA synthesis and cell replication; it is used to treat various cancers as well as autoimmune conditions such as rheumatoid arthritis and severe psoriasis. The combination of guselkumab plus methotrexate has been investigated for enhanced efficacy in inflammatory diseases such as psoriatic arthritis[3][5][6][7].
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