SEQUENCE
Trial question
Is risankizumab noninferior to ustekinumab in patients with moderate-to-severe Crohn's disease?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
49.0% female
51.0% male
N = 520
520 patients (253 female, 267 male)
Inclusion criteria: patients with moderate-to-severe Crohn's disease who had an inadequate response to or unacceptable side effects with anti-TNF therapy
Key exclusion criteria: current diagnosis of ulcerative colitis or indeterminate colitis; current known complications of Crohn's disease; prior exposure to p19 and/or p40 inhibitors; receipt of an approved biologic agent for Crohn's disease
Interventions
N=255 risankizumab (at an intravenous induction dose of 600 mg at weeks 0, 4, and 8, followed by a subcutaneous maintenance dose of 360 mg every 8 weeks from week 12 to week 48)
N=265 ustekinumab (a single weight-based intravenous induction dose of 260-520 mg at week 0, followed by a subcutaneous maintenance dose of 90 mg every 8 weeks, starting at week 8)
Primary outcome
Clinical remission at week 24
58.6
39.5
58.6 %
44.0 %
29.3 %
14.7 %
0.0 %
Risankizumab
Ustekinumab
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in clinical remission at week 24 (58.6% vs. 39.5%; AD 18.4%, 95% CI 6.6 to 30.3)
Secondary outcomes
Significant increase in endoscopic remission at week 48 (31.8% vs. 16.2%; AD 15.6%, 95% CI 8.4 to 22.9)
Significant increase in clinical remission at week 48 (60.8% vs. 40.8%; AD 19.7%, 95% CI 11.3 to 28.1)
Significant increase in corticosteroid-free endoscopic remission at week 48 (31.4% vs. 15.5%; AD 15.9%, 95% CI 8.8 to 23.1)
Safety outcomes
No significant differences in adverse events, severe adverse events, and adverse events leading to treatment discontinuation.
Conclusion
In patients with moderate-to-severe Crohn's disease who had an inadequate response to or unacceptable side effects with anti-TNF therapy, risankizumab was noninferior to ustekinumab with respect to clinical remission at week 24.
Reference
Laurent Peyrin-Biroulet, J Casey Chapman, Jean-Frederic Colombel et al. Risankizumab versus Ustekinumab for Moderate-to-Severe Crohn's Disease. N Engl J Med. 2024 Jul 18;391(3):213-223.
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