The use of risankizumab (brand name Skyrizi) in the treatment of adult patients with moderately to severely active Crohn‘s disease met the two primary endpoints in a head-to-head study compared to ustekinumab, its manufacturer AbbVie has announced.
While both risankizumab and ustekinumab are already approved for Crohn‘s disease and other conditions, their modes of action are different, with the former selectively blocking interleukin-23 (IL-23) signalling and the latter blocking both IL-12 and IL-23. The researchers therefore sought to determine if these differences affect treatment outcomes.
In the phase 3, multi-centre, randomised, head-to-head SEQUENCE study, the primary endpoint was non-inferiority for clinical remission at week 24 and superiority of endoscopic remission at week 48.
All participants had a confirmed diagnosis of Crohn‘s disease for at least three months and a Crohn‘s Disease Activity Index (CDAI) score of 220 to 450 at baseline. They were also considered to have moderate-to-severe disease based on an assessment of stool frequency, abdominal pain score, their Simple Endoscopy Score for Crohn‘s Disease (SES-CD), and a demonstrated intolerance or inadequate response to one or more anti-TNF therapies.
Participants assigned to risankizumab received a 600 mg intravenous induction at Weeks 0, 4 and 8 and 360 mg subcutaneous injection starting at week 12 and every eight weeks thereafter, through to week 48.
Risankizumab versus ustekinumab
The results of the first primary endpoint, clinical remission (per CDAI, defined as CDAI <150) at week 24, met non-inferiority of risankizumab versus ustekinumab (non-inferiority margin of 10%). Remission rates were 59% in the risankizumab group and 40% in the ustekinumab group.
For the second primary endpoint of endoscopic remission (SES-CD ≤4 and at least a two-point reduction versus baseline and no sub-score greater than 1 in any individual component) at week 48, risankizumab provided a remission rate of 32% compared to 16% in the ustekinumab group (p < 0.0001).
In a commentary of these results, Dr Laurent Peyrin-Biroulet, director of the Infinity Institute, professor of gastroenterology and head of the inflammatory bowel disease group at the gastroenterology department, University Hospital of Nancy in France, said: ‘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.’
Full results from the SEQUENCE study will be presented at a future medical meeting and submitted for publication in a peer-reviewed journal.