AT UEG WEEK 2023
COPENHAGEN – (CD) who have failed one or more anti–tumor necrosis factor (anti-TNF) therapies, according to the results of the phase 3 SEQUENCE trial.
Secondary endpoints – presented for the first time at the United European Gastroenterology Week 2023 – also showed superiority of risankizumab (Skyrizi, AbbVie), an interleulin-23 inhibitor, over ustekinumab (Stelara), an IL-12 and IL-23 inhibitor, for clinical remission at week 48 (60.8% vs. 40.8%) and a statistically significant endoscopic response also favoring risankizumab at weeks 24 and 48.
“With endoscopic remission we see that with a single agent we have doubled the endoscopic remission rate by moving from 16% to 31% with risankizumab [at week 48],” said Laurent Peyrin-Biroulet, MD, PhD, a gastroenterologist specializing in inflammatory bowel disease at Nancy University Hospital, France. “Superiority for sure was met.”
“This sort of thing happens once in your career,” noted Dr. Peyrin-Biroulet, who presented the results of the study at the meeting. “It’s totally amazing that everything you see here was in favor of risankizumab.
“Already we see the efficacy signal in the proportion of premature discontinuations at 2% vs. 13% due to lack of efficacy [in risankizumab and ustekinumab, respectively],” he said. “This is due to drug failure.”
Risankizumab is an IL-23 inhibitor that selectively blocks the cytokine IL-23, thought to be linked to a number of chronic immune-mediated diseases, by binding to its p19 subunit. It is the first IL-23 inhibitor to receive approval from the U.S. Food and Drug Administration in June 2022 for moderately to severely active CD based on data from the ADVANCE, MOTIVATE, and FORTIFY trials.
Risankizumab and ustekinumab head-to-head
The phase 3, open-label, multicenter, randomized, clinical trial evaluated risankizumab vs. ustekinumab through week 48 in patients with moderately to severely active CD.
Participants were required to have a CD Activity Index (CDAI) score of 220 to 450 at baseline, a Simple Endoscopic Score for Crohn’s Disease (SES-CD) of 6 or more for ileocolonic or colonic disease (and of 4 or more for isolated ileal disease), excluding the presence of a narrowing component, plus an average daily stool frequency of four or more and/or average daily abdominal pain score of 2 or more. They were also required to have previously failed one or more anti-TNF therapies.
Randomization was stratified by the number of anti-TNF therapies failed (one or more than one), and steroid use at baseline; steroids were then tapered from week 2. Two primary endpoints comprised clinical remission at week 24 (defined as CDAI < 150, noninferiority margin within 10% of risankizumab vs ustekinumab in 50% of participants), and also endoscopic remission (SES-CD of 4 or less, and at least a 2-point reduction vs. baseline and no subscore greater than 1 in any individual component) at week 48 demonstrating superiority of risankizumab vs ustekinumab.
Secondary endpoints included clinical remission at week 48, endoscopic response at weeks 48 and 24, steroid-free endoscopic remission at week 48, and steroid-free clinical remission at week 48 (all tested for superiority of risankizumab vs ustekinumab).
Intravenous risankizumab at 600 mg was given at weeks 0, 4 , and 8 followed by subcutaneous risankizumab at a 360-mg maintenance dose every 8 weeks through week 48 (n = 255). Participants who completed the week-48 visit continued on subcutaneous risankizumab for up to an additional 220 weeks. Ustekinumab was given as a weight-based, intravenous induction dose at week 0 followed by a 90-mg subcutaneous dose every 8 weeks, starting at week 8 through week 48 (n = 265). Participants received open-label drug administration but efficacy assessment was blinded.
