Risankizumab Bests Ustekinumab in Head-to-Head SEQUENCE Trial

Laurent Peyrin-Biroulet, MD, PhD

Credit: Image Analysis Group

AbbVie has announced positive topline results from the phase 3 SEQUENCE clinical trial evaluating risankizumab (Skyrizi) versus ustekinumab (Stelara) for the treatment of adult patients with moderately to severely active Crohn disease (CD), with risankizumab achieving all primary and secondary endpoints.¹

"Head-to-head studies like the SEQUENCE study are important in helping physicians understand differences in therapies and define treatment algorithms in clinical practice," said Laurent Peyrin-Biroulet, MD, PhD, director of the Infinity Institute, professor of gastroenterology and head of the inflammatory bowel disease group at the University Hospital of Nancy in Nancy, France.¹ "These results add to our growing body of evidence for [risankizumab] in Crohn's Disease. This study highlights the efficacy of [risankizumab] compared to ustekinumab in helping eligible patients achieve clinical and endoscopic treatment goals and also reinforces the safety profile observed in previous studies."

Announced on September 12, 2023, topline results from the trial come just more than a year after risankizumab became the first interleukin-23 (IL-23) inhibitor to receive approval from the US Food and Drug Administration (FDA) for moderately to severely active CD based on data from the ADVANCE, MOTIVATE, and FORTIFY trials.^1,2 A staple in armamentariums, the approval of ustekinumab, an IL-12 and IL-23 inhibitor, dates back to September 2016, when it became the first biologic therapy approved for CD targeting IL-12 and IL-23 cytokines.³

Risankizumab selectively blocks IL-23, a cytokine involved in inflammatory processes and thought to be linked to a number of chronic immune-mediated diseases, by binding to its p19 subunit. It is approved by the FDA for the treatment of plaque psoriasis, psoriatic arthritis, and CD.¹

A multicenter, randomized, head-to-head study, SEQUENCE evaluated the safety and efficacy of risankizumab and ustekinumab through week 48 in patients with CD who failed anti-TNF therapy. To be included in the study, patients were required to have a confirmed diagnosis of CD for at least 3 months, CD Activity Index (CDAI) score of 220-450 at baseline, confirmed diagnosis of moderate to severe CD assessed by stool frequency, abdominal pain score, and Simple Endoscopy Score for Crohn's Disease (SES-CD), and demonstrated intolerance or inadequate response to 1 or more anti-TNF therapies.¹

The September 12, 2023 release from AbbVie noted the trial achieved both primary endpoints for clinical remission at week 24 and endoscopic remission at week 48. Clinical remission results met non-inferiority of risankizumab versus ustekinumab with a 10% non-inferiority margin. Remission rates at week 24 were 59% in the risankizumab group and 40% in the ustekinumab group, with risankizumab use also associated with greater rates of endoscopic remission than ustekinumab at week 48 (32% vs 16%, respectively).¹

The release from Abbvie noted the trial also achieved statistically significant superiority for all secondary endpoints.¹ According to ClinicalTrials.gov, secondary endpoints for the trial included the percentage of patients achieving clinical remission at week 48, percentage of patients achieving endoscopic response at week 48, percentage of participants achieving endoscopic response at week 24, percentage of participants achieving steroid-free endoscopic remission, and percentage of participants achieving steroid-free clinical remission.⁴

Of note, AbbVie pointed out the safety profile of risankizumab in the SEQUENCE study appeared to be consistent with the known safety profile of risankizumab, with no new safety risks observed. The release detailed the most common adverse events, including COVID-19, headache, and CD for the risankizumab group and COVID-19, CD, and arthralgia for the ustekinumab group.¹

"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, MD, senior vice president of Development in Regulatory Affairs and chief medical officer at AbbVie.¹ "These head-to-head data reinforce SKYRIZI is an effective treatment option for patients living with Crohn's disease."

References

1. AbbVie. AbbVie's SKYRIZI® (risankizumab) Met All Primary and Secondary Endpoints Versus Stelara® (ustekinumab) in Head-to-Head Study in Crohn's Disease. Press Releases. September 12, 2023. Accessed September 12, 2023. https://news.abbvie.com/news/press-releases/abbvies-skyrizi-risankizumab-met-all-primary-and-secondary-endpoints-versus-stelara-ustekinumab-in-head-to-head-study-in-crohns-disease.htm
2. AbbVie. SKYRIZI® (risankizumab-rzaa) Receives FDA Approval as the First and Only Specific Interleukin-23 (IL-23) to Treat Moderately to Severely Active Crohn's Disease in Adults. News Center. June 17, 2022. Accessed September 12, 2023. https://news.abbvie.com/news/press-releases/skyrizi-risankizumab-rzaa-receives-fda-approval-as-first-and-only-specific-interleukin-23-il-23-to-treat-moderately-to-severely-active-crohns-disease-in-adults.htm
3. Johnson & Johnson. FDA Approves STELARA® (Ustekinumab) for Treatment of Adults With Moderately to Severely Active Crohn’s Disease. Innovation. September 26, 2016. Accessed September 12, 2023. https://www.jnj.com/media-center/press-releases/fda-approves-stelara-ustekinumab-for-treatment-of-adults-with-moderately-to-severely-active-crohns-disease
4. Clinicaltrials.gov. Study Comparing Intravenous (IV)/​Subcutaneous (SC) Risankizumab to IV/​SC Ustekinumab to Assess Change in Crohn's Disease Activity Index (CDAI) in Adult Participants With Moderate to Severe Crohn's Disease (CD) (SEQUENCE). Study Record. August 25, 2023. Accessed September 12, 2023. https://www.clinicaltrials.gov/study/NCT04524611