Ustekinumab versus risankizumab for Crohn’s disease
Peyrin-Biroulet L et al, N Engl J Med. 2024;391(3):213–23
Risankizumab was non-inferior to ustekinumab in achieving clinical remission after 24 weeks in patients with moderate-to-severe Crohn’s disease following failure of anti-TNF antibodies in this open-label head-to-head trial (SEQUENCE). However, risankizumab was significantly superior with respect to endoscopic remission after 48 weeks.
Background: The efficacy and safety of risankizumab as compared with ustekinumab in patients with Crohn's disease are unknown.
Methods: In this phase 3b, multicenter, open-label, randomized, controlled trial with blinded assessment of end points, patients with moderate-to-severe Crohn's disease who had had an inadequate response to anti-tumor necrosis factor therapy or unacceptable side effects with such therapy were randomly assigned to receive risankizumab or ustekinumab at standard doses for 48 weeks. The 2 primary end points, which were tested sequentially, were clinical remission at week 24 (defined as a Crohn's Disease Activity Index score of < 150 [range, 0–600, with higher scores indicating more severe disease activity]), which was analyzed in the first 50% of patients to complete the week-24 visit, with a non-inferiority margin of 10 percentage points; and endoscopic remission at week 48 (defined as a score of ≤ 4, a decrease of ≥ 2 points from baseline, and no subscore > 1 in any individual variable on the Simple Endoscopic Score for Crohn's Disease [range, 0–56, with higher scores indicating more severe disease]), which was analyzed for superiority in 100% of the patients. Safety was assessed in all patients who received at least 1 dose of risankizumab or ustekinumab.
Results: In the full intention-to-treat population for the efficacy analysis, 230 of 255 patients (90.2%) who received risankizumab and 193 of 265 patients (72.8%) who received ustekinumab completed all the assigned treatments. Both primary end points were met; risankizumab was non-inferior to ustekinumab with respect to clinical remission at week 24 (58.6% vs. 39.5%; adjusted difference, 18.4 percentage points; 95% confidence interval [CI]: 6.6–30.3) and superior to ustekinumab with respect to endoscopic remission at week 48 (31.8% vs. 16.2%; adjusted difference, 15.6 percentage points; 95% CI: 8.4–22.9; p < 0.001). The incidence of adverse events appeared to be similar in the 2 groups.
Conclusions: In this head-to-head clinical trial of risankizumab and ustekinumab involving patients with moderate-to-severe Crohn's disease who had had unacceptable side effects with anti-tumor necrosis factor therapy or an inadequate response to such therapy, risankizumab was non-inferior to ustekinumab with respect to clinical remission at week 24 and superior with respect to endoscopic remission at week 48.