Guselkumab: A New Therapeutic Option for the Treatment of Moderately to Severely Active Ulcerative Colitis.

Objective: To summarize the evidence and pharmacologic profile of guselkumab for moderate to severe ulcerative colitis (UC).

Data sources: A PubMed search from inception to end of October 2024 using keywords guselkumab, UC, and interleukin (IL) was conducted. Additional information was obtained from abstracts and package insert.

Study selection and data extraction: Phase 2/3 studies plus applicable literature on guselkumab pharmacologic and clinical profile were included.

Data synthesis: Approval was based on the QUASAR program, a multicenter, randomized, double-blind, placebo-controlled, phase 2b/3 trial assessing guselkumab's efficacy and safety in adults with moderately to severely active UC who had inadequate response or intolerance to conventional therapies, biologics (excluding IL antagonists), or Janus Kinase inhibitors. Results indicated that guselkumab led to higher clinical remission rates at week 12 and 44 compared to placebo, along with improvements in clinical response, symptomatic remission, endoscopic improvement, and histologic normalization. Common adverse effects included respiratory tract infections, injection site reactions, and arthralgia.

Relevance to patient care and clinical practice in comparison to existing drugs: Guselkumab is the fourth IL antagonist approved for UC, and the first to target CD64 (cells involved in IL-23 production). With its dual mechanism, guselkumab is hypothesized to neutralize IL-23 at production and reduce inflammatory response. The QUASAR findings suggest guselkumab can provide durable clinical remission and histologic normalization, addressing a significant gap in UC treatment.

Conclusion: As the latest addition to UC therapies, guselkumab presents improved efficacy and dosing flexibility without introducing any new safety concerns compared to existing agents.