Risankizumab Achieves Primary Endpoints over Ustekinumab in SEQUENCE Trial

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Announced by AbbVie on October 15, 2023, positive results revealed 59% of patients treated with risankizumab and 40% of patients treated with ustekinumab achieved clinical remission, respectively.

Laurent Peyrin-Biroulet, MD, PhD | Credit: Image Analysis Group

Laurent Peyrin-Biroulet, MD, PhD

Credit: Image Analysis Group

AbbVie has announced positive results from the head-to-head phase 3 SEQUENCE study evaluating the efficacy and safety of risankizumab (Skyrizi) compared to ustekinumab (Stelara) for patients with moderately to severely active Crohn disease (CD).

Announced on October 15, 2023, new data presented at the United European Gastroenterology Week 2023 showed risankizumab met both primary endpoints of non-inferiority for clinical remission at week 24 and superiority of endoscopic remission at week 48 versus ustekinumab.1

"The results from the SEQUENCE study provide physicians with important data to help inform therapy options that can help patients reach treatment goals," said Laurent Peyrin-Biroulet, MD, PhD, director of the Infinity Institute and head of the inflammatory bowel disease unit at Nancy University Hospital.1 "These findings reaffirm SKYRIZI as an efficacious interleukin-23 inhibitor that can support the achievement of stringent targets that contribute to improved care for patients."

Both IL-23 inhibitors, risankizumab and ustenkinumab have become staples in the management of multiple chronic inflammatory diseases since they received initial approvals from the FDA in 2019 and 2009, respectively. With risankizumab receiving approval for CD in 2022 and ustekinumab receiving a similar indication in 2016, many have hypothesized about the comparative benefits of the agents.1

A multicenter, randomized, head-to-head trial, SEQUENCE evaluated risankizumab compared to ustekinumab for the treatment of adults with moderate to severe CD. To be included in the study, participants were required to have a confirmed diagnosis of CD for at least 3 months prior to baseline, have a CD activity index (CDAI) score of 220-450 at baseline, and demonstrate intolerance or inadequate response to 1 or more anti-tumor necrosis factor (TNF) therapies.2

In total, 527 participants were enrolled in the study and randomized to risankizumab or ustekinumab. In part 1, participants assigned to risankizumab received intravenous doses of risankizumab at weeks 0, 4, and 8, and subcutaneous doses every 8 weeks through week 48. Participants assigned to ustekinumab received an intravenous dose of ustekinumab at Week 0 and subcutaneous doses every 8 weeks through week 48. In part 2, participants who received risankizumab in part 1 and completed the week 48 visit continued to receive subcutaneous risankizumab for up to an additional 220 weeks.2

The study had 2 primary endpoints, which were clinical remission at week 24 and endoscopic remission at week 48. Secondary endpoints included clinical remission at week 48, endoscopic response at weeks 24 and 48, steroid-free endoscopic remission at week 48, and steroid-free clinical remission at week 48.2

According to the release, 59% of patients treated with risankizumab achieved clinical remission compared to 40% of those using ustekinumab (P < .01). Additionally, 32% of patients in the risankizumab group achieved endoscopic remission compared to 16% in the ustekinumab group (P < .0001). Risankizumab also demonstrated superiority versus ustekinumab for the following ranked secondary endpoints:

  • 61% risankizumab compared to 41% ustekinumab for clinical remission at week 48
  • 45% risankizumab compared to 22% ustekinumab for endoscopic response at week 48
  • 45% risankizumab compared to 26% ustekinumab for endoscopic response at week 24
  • 31% risankizumab compared to 15% ustekinumab for steroid-free endoscopic remission at week 48
  • 61% risankizumab compared to 40% ustekinumab for steroid-free clinical remission at week 48

The safety profile of risankizumab in the SEQUENCE study was consistent with the known safety profile of risankizumab. The most common adverse events seen in risankizumab-treated patients were COVID-19, headache, and CD, while ustekinumab-treated patients most frequently experienced COVID-19, CD, and arthralgia. Serious adverse events occurred in 10% of the risankizumab group and 17% of the ustekinumab group.1

"At AbbVie, we are committed to developing medicines and generating evidence that advance care for people living with immune-mediated conditions, including inflammatory bowel diseases," said Roopal Thakkar, MD, senior vice president of development and regulatory affairs and chief medical officer at AbbVie.1 "Results such as these not only help differentiate SKYRIZI as an option for managing Crohn's disease, but also may help to evolve the field by further informing on therapeutic strategies for patients."

References:

  1. AbbVie. AbbVie's SKYRIZI® (risankizumab) Versus STELARA® (ustekinumab) Head-to-Head Study in Crohn's Disease Meets All Primary and Secondary Endpoints. Press Releases. October 15, 2023. Accessed October 16, 2023. https://news.abbvie.com/article_display.cfm?article_id=12621
  2. 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). September 28, 2023. Accessed October 16, 2023. https://www.clinicaltrials.gov/study/NCT04524611
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