Describe the Mechanism of Action of Guselkumab

In this medication review, Whitney Steinmetz, NP, from Presbyterian Medical Group in Albuquerque, New Mexico, explores the mechanism of action of Guselkumab, a promising monoclonal antibody therapy for inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD).

IBD is driven by chronic gastrointestinal inflammation, resulting from a complex interplay of genetic predisposition, environmental triggers, and immune system dysregulation. A crucial element in this inflammatory process is interleukin-23 (IL-23), a pro-inflammatory cytokine that promotes the differentiation, expansion, and survival of Th17 cells. These Th17 cells produce additional inflammatory cytokines, such as IL-17 and IL-22, which contribute to intestinal inflammation and disease progression.

Guselkumab, a monoclonal antibody therapy, specifically targets the p19 subunit of IL-23, preventing its interaction with the IL-23 receptor on T cells. By blocking IL-23 signaling, Guselkumab reduces Th17 cell activation and cytokine production, leading to a decrease in gut inflammation. This mechanism positions Guselkumab as a promising treatment option for IBD, aiming to mitigate chronic inflammation, improve mucosal healing, and enhance patient outcomes.

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