SEQUENCE: Skyrizi outperforms for Crohn’s remission; Stelara ‘still remains on the table’
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Key takeaways:
- More patients with Crohn’s disease who failed anti-TNF therapy achieved biologic remission with Skyrizi vs. Stelara.
- Skyrizi also demonstrated greater reduction in inflammatory biomarkers as early as 8 weeks.
WASHINGTON — Although a greater number of patients with Crohn’s disease who failed anti-TNF therapy achieved biologic remission with Skyrizi vs. Stelara, choosing between the two therapies “still remains on the table,” a researcher noted.
Skyrizi (risankizumab, AbbVie) previously demonstrated noninferiority for clinical remission at week 24, and superior endoscopic remission at week 48 compared with Stelara (ustekinumab, Janssen), as reported in the phase 3b SEQUENCE trial presented at UEG Week 2023. However, questions remained regarding the achievement of clinical remission and reduction in inflammatory biomarkers between the two drugs.
“When there are many treatment options and you are making a decision on which therapy to choose, placebo-controlled trials don’t give you insights compared to a drug on the market,” Marla C. Dubinsky, MD, chief of the division of pediatric gastroenterology and nutrition at Mount Sinai Kravis Children’s Hospital and co-director of the Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center, told Healio. “Head-to-head trials like SEQUENCE provide data to help us make patient-centered decisions about which treatment to offer patients. Placebo-controlled trials don’t match the real world as we don’t offer placebo to our patients.”
To establish the efficacy of risankizumab vs. ustekinumab for patients with CD in terms of biologic remission and baseline changes in inflammatory biomarkers, Dubinsky and colleagues conducted a post-hoc analysis of the open-label, multicenter SEQUENCE trial. The researchers examined baseline changes in fecal calprotectin (FCP) and high-sensitivity C-reactive protein at 8, 24 and 48 weeks using a mixed-effect model.
Additionally, Dubinsky and colleagues assessed biologic remission — defined as clinical remission (CDAI < 150) as well as FCP 250 mg/kg or high-sensitivity CRP 5 mg/L — as an efficacy endpoint at 24 and 48 weeks using non-responder imputation.
According to data presented at Digestive Disease Week, risankizumab demonstrated a greater reduction from baseline in FCP (–1,014 vs. –650.2) and high-sensitivity CRP (–10.6 vs. –5.5; P < .01) compared with ustekinumab as early as 8 weeks.
Additionally, a higher percentage of patients who received risankizumab vs. ustekinumab achieved biologic remission at weeks 8 (26.3% vs. 21.9%), 24 (42.8% vs. 24.9%) and 48 (46.3% vs. 27.5%).
“What needs to be pointed out is that this trial compared on-label dosing — every 8 weeks maintenance dosing — for both drugs,” Dubinsky told Healio. “While there is no data as of yet to suggest the need to dose-intensify risankizumab, there is substantial data on the need and benefit of every 4 weeks of ustekinumab, which was not the dosing used in this trial. So, the decision on escalating ustekinumab or switching to risankizumab still remains on the table.”
Dubinsky noted that future studies for risankizumab in CD should address perianal disease and post-operative prevention, as well as the effect of extraintestinal manifestations when selecting a drug sequence.
“Since many of our patients are presenting with primary or secondary loss of response to anti-TNF therapy, these results help guide us on what to use next,” Dubinsky said. “The name of the trial is quite fitting as it does help us sequence therapies. The data on clinical remission superiority, as well as greater improvement in biomarker response, is quite impressive and important.”
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Dubinsky MC, et al. Risankizumab vs. ustekinumab for the achievement of clinical remission and reduction in inflammatory biomarkers in patients with moderate to severe Crohn’s disease: Results from the phase 3b SEQUENCE trial. Presented at: Digestive Disease Week; May 18-21, 2024; Washington (hybrid).
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