Pair of Randomized Clinical Trials Show Skyrizi Improves Clinical Remission in Moderately to Severely Active Ulcerative Colitis

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An analysis of two randomized clinical trials (NCT03398148 and NCT03398135) found that Skyrizi (risankizumab; AbbVie, Boehringer Ingelheim) increased rates of clinical remission among patients with moderately to severely active ulcerative colitis (UC).^1-3

Skyrizi is a humanized immunoglobulin G1 monoclonal antibody that selectively binds to the p19 subunit of the interleukin (IL)-23 cytokine and inhibits its interaction with the IL-23 receptor. IL-23 is a naturally occurring cytokine that is involved in inflammatory and immune responses.

Skyrizi has been approved by the FDA and the European Medicines Agency to treat plaque psoriasis, psoriatic arthritis, and Crohn disease, with Phase III trials ongoing for psoriasis, psoriatic arthritis, Crohn disease, and UC.⁴ The authors of the study, published online by JAMA, compared the efficacy and safety of Skyrizi vs. placebo both as an induction and a maintenance therapy in the treatment of patients with UC.

“The cytokine IL-23 is implicated in intestinal inflammation and ulcerative colitis pathogenesis, and it stimulates the proliferation of inflammatory cell populations and supports the activation of other cytokines, including IL-17 and IL-22,” the study authors wrote. “Ustekinumab, which targets the p40 subunit shared between IL-12 and IL-23, and mirikizumab, which targets the p19 subunit specific to IL-23, have previously demonstrated the therapeutic potential of this pathway in ulcerative colitis. [Skyrizi] is a monoclonal IgG-1 antibody that selectively targets the IL-23 p19 subunit, blocking signaling through the IL-23 receptor.”¹

Investigators enrolled 977 patients in the induction trial, which was conducted at 261 clinical centers from November 5, 2020, to August 4, 2022, with a final follow-up on May 16, 2023. A total of 754 patients were enrolled in the maintenance trial, which was conducted at 238 clinical centers from August 28, 2018, to March 30, 2022, with a final follow-up on April 11, 2023.

Eligibility criteria included moderately to severely active UC; a history of intolerance or inadequate response to one or more conventional therapies, advanced therapies, or both; and no previous treatment history with Skyrizi.

Patients in the induction trial were randomly assigned in a 2:1 ratio to receive 1200 mg of Skyrizi or placebo, administered intravenously (IV) at weeks zero, four, and eight. Patients in the maintenance trial who achieved a clinical response following IV treatment with Skyrizi were randomly assigned in a 1:1:1 ratio to receive subcutaneous (SC) administration of 180 mg or 360 mg Skyrizi or placebo every eight weeks for 52 weeks.

The trial’s primary outcome was clinical remission—with a stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability—at week 12 in the induction trial and at week 52 in the maintenance trial.

At week 12 of the induction trial, clinical remission rates among the 975 patients enrolled were 20.3% in the 1200 mg Skyrizi cohort and 6.2% in the placebo cohort, with an adjusted between-group difference of 14.0% (95% CI, 10.0%-18.0%, P < .001). For the maintenance trial, clinical remission rates at week 52 among the 548 patients enrolled were 40.2% in the 180 mg Skyrizi cohort, 37.6% in the 360 mg Skyrizi cohort, and 25.1% in the placebo cohort, with an adjusted between-group difference of 16.3% for 180 mg Skyrizi compared to placebo (97.5% CI, 6.1%-26.6%), P < .001) and an adjusted between-group difference of 14.2% for 360 mg Skyrizi vs. placebo (97.5% CI, 4.0%-24.5%, P = .002).

In terms of safety, there were no new adverse event signals reported among the treatment groups.

“In the phase 3 induction and maintenance trials, treatment with [Skyrizi] improved rates of clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis,” the study authors wrote. “In the induction trial, treatment with [Skyrizi] improved endoscopic and histological secondary outcomes characterized by endoscopic improvement; endoscopic remission; and histological, endoscopic, and mucosal improvement. These improvements were also observed in the maintenance trial.”¹

References

1. Louis E, Schreiber S, Panaccione R, et al. Risankizumab for Ulcerative Colitis: Two Randomized Clinical Trials. JAMA. Published online July 22, 2024. doi:10.1001/jama.2024.12414

2. A Multicenter, Randomized, Double-Blind, Placebo Controlled Induction Study to Evaluate the Efficacy and Safety of Risankizumab in Participants With Moderately to Severely Active Ulcerative Colitis. ClinicalTrials.gov. August 1, 2023. https://www.clinicaltrials.gov/study/NCT03398148?id=NCT03398148&rank=1

3. A Study to Assess the Efficacy and Safety of Risankizumab in Participants With Ulcerative Colitis. ClinicalTrials.gov. June 18, 2024. https://www.clinicaltrials.gov/study/NCT03398135?id=NCT03398135&rank=1

4. Risankizumab (Skyrizi) achieves primary and all secondary endpoints in phase 3 induction study in patients with ulcerative colitis. News release. AbbVie. March 23, 2023. Accessed July 24, 2024. https://news.abbvie.com/news/press-releases/risankizumab-skyrizi-achieves-primary-and-all-secondary-endpoints-in-phase-3-induction-study-in-patients-with-ulcerative-colitis.htm