Oct. 01, 2025
Interleukin 23 (IL-23) is a cytokine that plays a key role in the immune system and inflammation. Because individuals with inflammatory bowel disease (IBD) have been shown to have higher circulating levels of IL-23 when compared with healthy controls, researchers hypothesize that IL-23 is involved in the inflammatory process that occurs in Crohn's disease (CD).
Risankizumab (RZB) is a humanized monoclonal immunoglobulin antibody that selectively inhibits IL-23. Multiple phase 3 clinical trials have demonstrated that RZB induces and maintains remission in patients with moderately to severely active CD.
Building on this knowledge, a team of researchers conducted a multicenter retrospective cohort study to evaluate the effectiveness and safety of RZB in a real-world population of individuals with CD, including patients who were previously treated with ustekinumab (UST) and other advanced therapies. The study involved patients from eight IBD centers across the United States, and the results were published in the Journal of Crohn's and Colitis in 2025.
Methods
The researchers identified 309 adult patients with a confirmed diagnosis of CD who were treated with RZB and had at least 12 weeks of follow-up. Patient data were obtained from a consortium including Mayo Clinic in Rochester, Minnesota; Washington University in St. Louis; Cedars-Sinai Medical Center in Los Angeles; Icahn School of Medicine at Mount Sinai in New York City; Baylor College of Medicine in Houston; Brooke Army Medical Center in San Antonio; University of Michigan in Ann Arbor, Michigan; and Albert Einstein College of Medicine in New York City.
Primary outcomes were week 12 clinical remission rates and six-month endoscopic remission rates. Clinical remission was defined as a Harvey Bradshaw Index (HBI) score of 4 or higher or physician global assessment in those without HBI scores or with ileostomy. Endoscopic remission was defined as a Simplified Endoscopic Mucosal Assessment for CD (SEMA-CD) score of 0 to 1 or absence of ulcers.
Results and conclusions
According to Amanda M. Johnson, M.D., real-world data in studies such as this help provide additional data on the effectiveness and safety of RZB in a more heterogenous population of patients outside of the more restrictive clinical trial settings — and in patients who are more heavily exposed to multiple advanced therapies. Dr. Johnson served as the lead author on the study publication and is a gastroenterologist and researcher at Mayo Clinic in Rochester, Minnesota.
"One of the more relevant and interesting clinical questions that was evaluated in this study was whether patients with prior exposure to ustekinumab, an IL-12/23 inhibitor, would still respond to risankizumab given its similar mechanism of action," explains Dr. Johnson. "What we found was that patients who were previously treated with ustekinumab still achieved similar rates of clinical remission, but that rates of endoscopic remission were lower when compared to those who had no prior ustekinumab exposure.
"Despite this, the endoscopic remission rates seen in those with prior ustekinumab exposure were still comparable to what was seen in the pivotal trials of risankizumab in Crohn's. Thus, we concluded that previous treatment with ustekinumab should not necessarily limit future use of risankizumab in patients with Crohn's disease."
Key findings include the following:
- 85.8% of patients were previously exposed to advanced therapy and 54.7% had prior UST exposure.
- Rates of clinical remission achieved at 12 weeks in patients with available follow-up data: 49.7% of the entire cohort; 44.2% of patients with UST exposure; and 57.1% of patients without UST exposure.
- Among patients with active disease identified at baseline endoscopy who had available six-month follow-up data, 52.4% achieved endoscopic remission.
- Cumulative rates of clinical and endoscopic remission for the entire cohort at 12 months were 65.0% and 49.5%, respectively.
- Cumulative rates of endoscopic remission at 12 months were 33.9% in patients with UST exposure and 68.1% in patients without UST exposure.
"Our study found that one of the strongest predictors of achieving clinical remission with risankizumab was the number of previously used advanced therapies for Crohn's disease that patients received," says Dr. Johnson. "This observation reflects a broader trend seen across the spectrum of IBD treatments: The greater the number of prior therapeutic failures, the lower the likelihood of response to subsequent therapies. To help combat this, additional research is needed to better understand the most appropriate sequencing of different therapies, as well as, ideally, to develop predictive biomarkers that identify which patients are most likely to respond to certain therapies up front."
"Our study found that one of the strongest predictors of achieving clinical remission with risankizumab was the number of previously used advanced therapies for Crohn's disease that patients received."
For more information
Johnson AM, et al. A multicenter study of the real-world effectiveness and safety of risankizumab in Crohn's disease. Journal of Crohn's and Colitis. In press.
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