Positioning Guselkumab in The Treatment Algorithm for Ulcerative Colitis

Ulcerative colitis is a chronic inflammatory bowel disease requiring long-term therapeutic strategies that balance efficacy, safety and durability/ persistence. As treatment targets have evolved toward deep remission, including clinical, endoscopic and histologic healing, there remains un unmet need for therapies that provide sustained benefit with selective immunomodulation. Interleukin-23 (IL-23) plays a central role in Th17-mediated mucosal inflammation, making selective IL-23p19 inhibition an attractive approach. Guselkumab, a fully human monoclonal antibody targeting IL-23p19, has demonstrated consistent efficacy and a favorable safety profile in Phase II and III clinical trials for moderate-to-severe UC. Data from the QUASAR and ASTRO programs show significant improvements in clinical, endoscopic, histologic and various quality of life (eg fatigue, urgency) outcomes during both induction and maintenance, with durable responses, corticosteroid-sparing effects, and efficacy across biologic-naïve and biologic-experienced populations. Emerging evidence also suggests a potential role of guselkumab within advanced combination strategies, although this approach remains investigational. This review summarizes the mechanistic rationale, pivotal clinical evidence, and practical considerations informing the positioning of guselkumab within contemporary UC treatment algorithms.