Efficacy and Safety of Guselkumab for Ulcerative Colitis

Pipul Poudel , Arpana Khanal , Roshim Shrestha , Krishal Adhikari , Anastasia Thapa Magar , Faiza Ahmed* and Endrit Shahini

Abstract

Introduction: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by relapsing–remitting colonic inflammation, where biologic therapies targeting tumor necrosis factor (TNF), integrins, and interleukin (IL) pathways are widely used. Despite available options, a substantial proportion of patients fail to achieve sustained disease remission. Guselkumab, a fully human monoclonal antibody targeting the IL-23p19 subunit, has recently emerged as a novel therapeutic option.
Methods: We reviewed available evidence from phase II/III clinical trials, real-world data, and indirect comparisons evaluating the efficacy, safety, and tolerability of guselkumab in patients with moderate-to-severe UC. Outcomes of interest included clinical remission, endoscopic improvement, health-related quality of life, and incidence of adverse events. Comparisons with established biologics (e.g., infliximab, adalimumab, vedolizumab, ustekinumab, and golimumab) were summarized.
Results: The Phase IIb QUASAR study demonstrated significantly higher rates of clinical remission with guselkumab compared to placebo at week 12 (21% vs. 9%; p<0.05)
and sustained efficacy through maintenance therapy (34% vs. 21% at week 44). Endoscopic improvement and histologic remission were also superior in the guselkumab arm. Safety analyses revealed a favorable profile, with low rates of serious infections, malignancies, and major adverse cardiovascular events. Indirect comparisons suggest that the efficacy and safety of this agent are comparable or superior to those of other IL-23 inhibitors and anti-TNF agents, including golimumab, although head-to-head studies are lacking.
Conclusion: Guselkumab is a promising addition to the therapeutic armamentarium for moderate-to-severe UC, offering durable efficacy and a favorable safety profile. Comparative analyses position guselkumab alongside established therapies such as anti-TNFs, anti-α4β7 integrin, and IL-12/23 inhibitors, offering a compelling option in the expanding IL-23 inhibitor class. Further long-term studies and direct comparative trials are warranted to better define its positioning relative to other advanced therapies.

Keywords

Ulcerative Colitis, Guselkumab, Interleukin-23, Biologics, Efficacy, Safety, Golimumab, Inflammatory Bowel Disease

Corresponding Author

: Faiza Ahmed, Division of Clinical and Translational Research, Larkin Community Hospital, South Miami, Florida, United States of America.

Citation

Poudel, P., Khanal, A., Shrestha, R., Adhikari, K., Ahmed, F., et al. (2025). Efficacy and Safety of Guselkumab for Ulcerative Colitis. Med Pharmacol Open Access , 1(1), 01-13.