Guselkumab Achieves Clinical, Endoscopic Remission in Ulcerative Colitis

David T. Rubin, MD

Credit: University of Chicago

First-time data from the Phase 3 QUASAR Maintenance Study revealed patients with moderately to severely active ulcerative colitis (UC) met the primary endpoint of clinical remission with subcutaneous guselkumab (TREMFYA) treatment.¹

Presented at Digestive Disease Week (DDW) 2024, the results showed 50.0% (P <.001) of patients receiving guselkumab 200 mg every 4 weeks (Q4W) and 45.2% (P <.001) of patients receiving guselkumab 100 mg every 8 weeks (Q8W) achieved clinical remission at Week 44, compared with only 18.9% of placebo-treated patients.

All major secondary endpoints were met with guselkumab in UC—67% and 71% of these patients in clinical remission also reached highly statistically significant endoscopic remission (Mayo endoscopic subscore [MES], 0) at Week 44.

“These data suggest the potential of guselkumab to provide durable, clinical remission and improve important high-bar endpoints, such as endoscopic remission to the point of normalization and histologic remission, which represent the kind of progress needed in new treatments for this inflammatory bowel disease,” lead investigator David T. Rubin, MD, the chief of the section of gastroenterology, hepatology, and nutrition at the University of Chicago, said in a statement.²

Guselkumab marked the first FDA-approved, fully human dual-acting monoclonal antibody that blocks the cytokine IL-23, by binding to the p19 subunit of IL-23 and CD64, a receptor on cells producing IL-23.² IL-23 has been identified as a factor in the pathogenesis of autoimmune inflammatory diseases, including inflammatory bowel disease, of which UC is a main clinical form.³

The Phase 3 QUASAR Maintenance Study evaluated adults with UC who exhibited a clinical response to 12 weeks of guselkumab in Phase 2 and Phase induction studies in the QUASAR Phase 2b/3 trial program.¹ These patients were randomized 1:1:1 to receive subcutaneous guselkumab 200 mg every 4 weeks, guselkumab 100 mg every 8 weeks, or placebo.

Safety results revealed the number of patients with ≥1 adverse event was similar across the treatment groups: guselkumab 200mg Q4W (70%), guselkumab 100mg Q8W (64.5%), and placebo (68.2%). The most common events in the combined guselkumab group, compared with placebo, were COVID-19 (11.2% vs. 14.1%), UC (11.2% vs. 39.7%), and joint pain (6.1% vs. 6.8%), respectively.

Overall, the safety profile of guselkumab remained consistent with observations in the current FDA-approved indications of moderate to severe plaque psoriasis (PsO) and active psoriatic arthritis (PsA). According to the release, these clinical results indicate the promise of guselkumab treatment in managing challenging symptoms of UC that impact a patient’s daily life.

“The phase 3 QUASAR Maintenace study continues to demonstrate the promise of [guselkumab] to unlock potential treatment options for patients living with ulcerative colitis who continue to experience debilitating symptoms despite the availability of treatments today,” David Lee, MD, PhD, global therapeutic area head of immunology at Johnson & Johnson, said in a statement.²

References

1. _{Yeo YH, Rezaie A, Hsieh TY, Hu X, Mohamed G, Lee GY, Huang PC, Watson R, Gaddam S, Ma KS. The Efficacy and Safety of Guselkumab as Maintenance Therapy in Patients with Moderately to Severely Active Ulcerative Colitis: Results from the Phase 3 QUASAR Maintenace Study. Lecture presented at Digestive Disease Week 2024, May 18 - 21, 2024.}
2. _{Johnson & Johnson. Tremfya® (guselkumab) quasar maintenance study in UC met its primary endpoint and all major secondary endpoints, including highly statistically significant rates of endoscopic remission. PR Newswire: press release distribution, targeting, monitoring and marketing. May 20, 2024. Accessed May 20, 2024.}
3. _{Korta A, Kula J, Gomułka K. The Role of IL-23 in the Pathogenesis and Therapy of Inflammatory Bowel Disease. Int J Mol Sci. 2023;24(12):10172. Published 2023 Jun 15. doi:10.3390/ijms241210172}