An evaluation of guselkumab for the treatment of ulcerative colitis

INTRODUCTION: Interleukin (IL)-23 is a cytokine implicated in the pathogenesis of ulcerative colitis (UC). Guselkumab, a selective IL-23 antagonist, was approved for the treatment of moderately-to severely active UC in 2024/5. AREAS COVERED: The review briefly summarizes the pathophysiology of the IL-23 pathway and summarizes the available evidence on the efficacy and safety of guselkumab in UC. We discuss future challenges and clinical dilemmas in the use of guselkumab. EXPERT OPINION: Guselkumab has demonstrated efficacy across all endpoints with a favorable safety profile. No direct comparisons are available between individual IL-23 antagonists or with ustekinumab, the IL-12/23 antagonist, which limits decision-making in clinical practice. Combining two biologics as advanced combination treatment is an attractive strategy to break the therapeutic efficacy ceiling in UC - a proof-of-concept phase 2 trial combining guselkumab and golimumab has shown promise, the combination is currently undergoing evaluation in a larger ongoing trial.