Risankizumab Shows Superior Efficacy in Refractory Crohn's Disease Patients After Ustekinumab Failure
Key Insights
Patients with refractory Crohn's disease (search) who previously failed ustekinumab treatment demonstrated significant clinical and endoscopic improvements when treated with risankizumab.
Post-hoc analysis of phase 3 ADVANCE and MOTIVATE trials showed risankizumab achieved clinical remission rates of 37.2% and 36.1% respectively, compared to 15.8% and 10% with placebo.
Retrospective real-world data confirmed risankizumab's superiority over vedolizumab, with 80% vs 60% clinical response rates at 52 weeks and fewer treatment discontinuations.
Patients with refractory Crohn's disease (search) who previously received ustekinumab experienced significant clinical and endoscopic improvements with risankizumab, according to new data presented at the ACG Annual Scientific Meeting. The findings demonstrate that risankizumab remains effective even in patients who have failed multiple biologic therapies, including ustekinumab.
Post-Hoc Analysis Reveals Sustained Efficacy
Dr. Jessica R. Allegretti, medical director of the Crohn's and Colitis Center at Brigham and Women's Hospital and associate professor of medicine at Harvard Medical School, presented results of a post-hoc analysis examining risankizumab's efficacy among patients with refractory disease who previously failed ustekinumab.
"My general assumption was that patients exposed to ustekinumab will still respond to risankizumab," Allegretti told Healio. "We know that this agent has been found to be superior to ustekinumab in previous studies, like the SEQUENCE trial. The mechanisms are actually different enough that there is biologic plausibility why you should still respond to an IL-23 (search) inhibitor like risankizumab."
The analysis drew data from the phase 3 ADVANCE (n = 62) and MOTIVATE (n = 76) trials, both of which included patients with moderate to severe Crohn's disease (search) and intolerance or inadequate response to at least one biologic. Most patients had previously failed three or more biologics, and more than 90% had failed anti-tumor necrosis factor (search) therapy and/or vedolizumab.
Strong Clinical Outcomes Across Multiple Endpoints
Participants received 12 weeks of 600 mg IV risankizumab induction or placebo, and responsive patients were randomly assigned in the FORTIFY maintenance trial to 52 weeks of subcutaneous risankizumab 180 mg or 360 mg or placebo.
Results showed significantly more patients who received induction with 600 mg IV risankizumab versus placebo achieved clinical remission (ADVANCE: 37.2% vs 15.8%; MOTIVATE: 36.1% vs 10%), reduction in stool frequency/abdominal pain (ADVANCE: 25.6% vs 10.5%; MOTIVATE: 19.4% vs 10%) and endoscopic response (ADVANCE: 22.3% vs 5.4%; MOTIVATE: 19.5% vs 5%).
At 52 weeks, risankizumab 180 mg or 360 mg also outperformed placebo, with more patients achieving clinical remission (33.3% or 51.4% vs. 20%), reduction in stool frequency/abdominal pain (33.3% or 48.6% vs. 20%) and endoscopic response (33.3% or 29.4% vs. 20%).
Real-World Evidence Supports Superior Performance
Additional data presented at the meeting reinforced risankizumab's effectiveness through a retrospective analysis comparing risankizumab, vedolizumab, and upadacitinib in 291 adults with active Crohn's disease (search) at a large academic center.
Dr. Rahul S. Dalal, gastroenterologist and inflammatory bowel disease specialist at Brigham and Women's Hospital, led the study which showed that the risankizumab cohort (n = 152) achieved significantly greater clinical response at 52 weeks compared with the vedolizumab cohort (80% vs. 60%; P < .01). The risankizumab group also demonstrated fewer treatment discontinuations (18% vs. 32%; P = .02) and fewer adverse events (20% vs. 33%; P = .04) over 52 weeks.
Patients in the vedolizumab cohort had significantly lower odds of clinical response at 12 weeks (OR = 0.51) and 52 weeks (OR = 0.32), steroid-free clinical remission at 52 weeks (OR = 0.44), and endoscopic response (OR = 0.28) compared with the risankizumab cohort. They also faced significantly greater risk for treatment discontinuation (HR = 2.18; P = .01).
Safety Profile Remains Favorable
The most common adverse events in the vedolizumab cohort included infections (50%) and arthralgia (25%). The upadacitinib and risankizumab cohorts also experienced infections (26.9% and 40.6%), as well as rashes (38.5% and 15.6%). Researchers observed no new safety signals for any of the three agents.
Clinical Implications for Treatment Sequencing
"It's further evidence that adds to the literature supporting what I think we all already felt to be true," Allegretti said. "The biggest take-home point to me is that confidence level that physicians can now have in using this agent quite effectively in an ustekinumab-failure population, because I still think that that often had been a lingering question."
Dalal emphasized the need for larger prospective studies to confirm these findings. "I wouldn't change my prescribing habits based off of these data alone, but they do show us what the signals might be," he noted. "We need larger studies to confirm these findings."