AbbVie's IL-23 Inhibitor Risankizumab Demonstrates Superior Efficacy Over Ustekinumab in Crohn’s Disease Phase 3 SEQUENCE Trial

▎Edited by the WuXi AppTec content team

Recently, AbbVie announced the positive results of the head-to-head Phase 3 SEQUENCE study,This study evaluated the efficacy and safety of the interleukin-23 (IL-23) inhibitor risankizumab (brand name: Skyrizi) compared with active control drugs in patients with moderate to severe active Crohn's disease who had failed one or more anti-tumor necrosis factor (TNF) therapies.

Crohn's disease is a chronic systemic condition characterized by inflammation in the gastrointestinal tract, leading to persistent diarrhea and abdominal pain.. This is a progressive disease, which meansA significant portion of patients will experience worsening conditions over time, or develop complications that require emergency treatment, including surgical intervention.。Since the symptoms and signs of Crohn's disease are unpredictable, it imposes tremendous physical, emotional, and financial stress on patients.

Risankizumab is an IL-23 inhibitor that selectively blocks IL-23 by binding to the p19 subunit of IL-23.IL-23 is a cytokine involved in the inflammatory process and is considered to be associated with various chronic immune-mediated diseases. Risankizumab has been approved by the US FDA and the European Medicines Agency for the treatment of plaque psoriasis, psoriatic arthritis, and Crohn's disease. Currently, phase 3 trials of risankizumab for the treatment of psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis are underway.

Image Source: 123RF

SEQUENCE study includes two primary endpoints tested sequentially:

The first primary endpoint is clinical remission at week 24 (defined as the Crohn's Disease Activity Index [CDAI] total score

The results showed that risankizumab was non-inferior to the active comparator ustekinumab (brand name: Stelara) (pre-specified non-inferiority margin was 10%); the remission rate was 59% in the risankizumab group and 40% in the active comparator group. Researchers also conducted a post-hoc analysis on this endpoint to test for superiority, achieving a significant result with a p-value of less than 0.01.

The second major endpoint was endoscopic remission at week 48 (Simple Endoscopic Score for Crohn’s Disease [SES-CD] ≤4 points, with a reduction of at least 2 points from baseline, and no individual subscore exceeding 1 point).The results showed that the remission rate of risankizumab was 32%, and that of the active control drug was 16%.

Image Source: 123RF

Moreover, risankizumab was superior to the active comparator across all secondary endpoints, including clinical remission at week 48, endoscopic remission at weeks 48 and 24, steroid-free endoscopic remission at week 48, and steroid-free clinical remission at week 48.

The safety of risankizumab in the SEQUENCE study was consistent with its known safety profile, and no new safety risks were observed.Serious adverse events occurred in 10% of risankizumab-treated patients and 17% of active comparator patients.