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Risankizumab (Skyrizi) resulted in more clinical remissions compared with ustekinumab (Stelara) in adults with moderate to severe Crohn's disease who had failed at least one previous tumor necrosis factor (TNF) inhibitor, the phase IIIb SEQUENCE trial showed.

Clinical remission, based on a Crohn's Disease Activity Index (CDAI) score under 150, occurred in 59.6% of patients who received risankizumab versus 42.6% of those who received ustekinumab at 24 weeks (P=0.0001), and in 60.8% and 40.8%, respectively, at 48 weeks (P<0.0001), reported Marla C. Dubinsky, MD, of the Icahn School of Medicine at Mount Sinai in New York City, during the European Crohn's and Colitis Organisation Congress.

In addition, clinical remission based on an average daily stool frequency ≤2.8 and not worse than baseline and an average daily abdominal pain score ≤1 and not worse than baseline occurred in 55.7% of risankizumab patients compared with 41.1% of ustekinumab patients (P<0.001). This difference also persisted at 48 weeks (58.4% vs 36.6%, P<0.0001).

Meanwhile, clinical response occurred in 69.8% of risankizumab patients and 54.3% of ustekinumab patients (P<0.001) at week 24, and in 67.5% and 46.8%, respectively, at week 48 (P<0.0001).

"These results are important because they provide physicians with data to help inform treatment decisions to help their patients," Dubinsky told 名媛直播. "If a patient has failed at least one anti-TNF treatment and a physician is trying to decide which treatment makes sense as the next option, these findings may help the physician make that important decision. Overall, we hope these important data will contribute to improved care for patients."

Risankizumab is an interleukin (IL)-23 p19 inhibitor that was approved for the treatment of adults with moderately to severely active Crohn's disease in June 2022, while ustekinumab is an IL-12/23 p40 inhibitor that has been approved for the same patient population .

In October 2023, presented at United European Gastroenterology Week showed that risankizumab met the noninferiority endpoint at 24 weeks for CDAI clinical remission in 50% of patients: 58.6% for risankizumab versus 39.5% for ustekinumab. At week 48, endoscopic remission occurred in 31.8% of risankizumab patients compared with 16.2% of ustekinumab patients.

"It is unclear whether targeting IL-23 only has a clear biological rationale over IL-12 and IL-23, and more work needs to be done," Dubinsky said. "It is possible that we finally got the right exposure response and the advance is driven by dose. The same benefit for targeting IL-23 only was seen in psoriasis as well, so perhaps it is indeed the mechanism of action."

The enrolled 527 adults who had been diagnosed with Crohn's disease at least 3 months before the study began and who had an intolerance or inadequate response to at least one previous anti-TNF agent. The participants had a CDAI of 220 to 450; a Simple Endoscopic Score for Crohn's of at least 6, or 4 for isolate ileal disease; and an average daily stool frequency of at least 4 or an average daily abdominal pain score of at least 2. The final analysis included 520 participants, stratified by the number of previous TNF inhibitors they had failed and use of corticosteroids at baseline.

One arm of 255 patients received 600 mg of intravenous risankizumab at weeks 0, 4, and 8, and then 360 mg of subcutaneous risankizumab every 8 weeks through week 48. The other 265 patients received a baseline intravenous ustekinumab dose according to their weight at week 0 and then 90 mg of subcutaneous ustekinumab every 8 weeks. Any participants in both groups who were taking steroids began a mandatory steroid taper at week 2.

A post-hoc analysis showed that 60.8% of patients in the risankizumab group had a CDAI clinical response of at least 100 fewer points from baseline at week 8, compared with 51.3% of ustekinumab patients (P<0.05), with an adjusted treatment difference of 9.4 (95% CI 1.0-17.9). Clinical remission rates based on a CDAI score of less than 150 or based on stool frequency/abdominal pain score were not significantly different between the treatment groups at week 8.

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