AbbVie's SKYRIZI® (risankizumab) has demonstrated significant efficacy in treating Crohn's disease, according to top-line results from the Phase 3 SEQUENCE clinical trial. The head-to-head study compared risankizumab to STELARA® (ustekinumab) in adult patients with moderately to severely active Crohn's disease who had previously failed one or more anti-TNF therapies. The trial's findings highlight risankizumab's potential as a superior treatment option for this patient population.
The SEQUENCE study (study drug open-label and efficacy assessment blinded) evaluated risankizumab (600 mg intravenous [IV] induction at weeks 0, 4, and 8, followed by 360 mg subcutaneous injection [SC] every 8 weeks) against ustekinumab (IV dose at week 0, followed by 90 mg SC every 8 weeks) through week 48.
Primary Endpoint Achievements
The study met its first primary endpoint, demonstrating non-inferiority of risankizumab versus ustekinumab in achieving clinical remission (defined as Crohn's Disease Activity Index [CDAI] <150) at week 24. Remission rates were 59% in the risankizumab group and 40% in the ustekinumab group.
Risankizumab also met the second primary endpoint, showing superiority over ustekinumab in endoscopic remission (SES-CD ≤4 and at least a 2-point reduction versus baseline, with no sub-score greater than 1 in any individual component) at week 48. The remission rates were 32% in the risankizumab group and 16% in the ustekinumab group (p < 0.0001).
Secondary Endpoint Outcomes
All secondary endpoints achieved statistical significance for superiority versus ustekinumab, further supporting the efficacy of risankizumab in managing Crohn's disease.
Safety Profile
The safety profile of risankizumab in the SEQUENCE study was consistent with its known safety profile, and no new safety risks were identified. The most common adverse events reported were COVID-19, headache, and Crohn's disease in the risankizumab group, and COVID-19, Crohn's disease, and arthralgia in the ustekinumab group.
Expert Commentary
"We are encouraged by these results, which demonstrate the impact SKYRIZI can have in helping patients achieve both clinical and endoscopic remission," said Roopal Thakkar, senior vice president, development and regulatory affairs and chief medical officer, AbbVie. "These head-to-head data reinforce SKYRIZI is an effective treatment option for patients living with Crohn's disease."
Laurent Peyrin-Biroulet, M.D., Ph.D., director of the Infinity Institute, professor of gastroenterology and head of the Inflammatory Bowel Disease group at the Gastroenterology Department, University Hospital of Nancy, France, added, "Head-to-head studies like the SEQUENCE study are important in helping physicians understand differences in therapies and define treatment algorithms in clinical practice. These results add to our growing body of evidence for SKYRIZI in Crohn's Disease. This study highlights the efficacy of SKYRIZI compared to ustekinumab in helping eligible patients achieve clinical and endoscopic treatment goals and also reinforces the safety profile observed in previous studies."
About the SEQUENCE Study
The SEQUENCE study is a Phase 3, multicenter, randomized, head-to-head trial designed to evaluate risankizumab versus ustekinumab for treating adults with moderate to severe Crohn's disease who have a history of inadequate response or intolerance to one or more anti-TNF therapies. Participants had a confirmed Crohn's disease diagnosis for at least 3 months, a CDAI score between 220 and 450 at baseline, and demonstrated intolerance or inadequate response to anti-TNF therapies.
About Risankizumab (SKYRIZI®)
Risankizumab (SKYRIZI®) is an interleukin-23 (IL-23) inhibitor that selectively blocks IL-23 by binding to its p19 subunit. IL-23 is a cytokine involved in inflammatory processes and is linked to chronic immune-mediated diseases. SKYRIZI is approved for treating plaque psoriasis, psoriatic arthritis, and Crohn's disease. Phase 3 trials are ongoing for risankizumab in psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis.
Full results from the SEQUENCE study will be presented at a future medical meeting and submitted for publication in a peer-reviewed journal.
