Chief of the Digestive Disease Institute
Cleveland Clinic, Cleveland
There are now many approved treatments for inflammatory bowel disease, which have been major advances for our patients and our field, in the United States and around the world. In many cases, new medications are compared with placebo, rather than head-to-head.
The first study in this month’s report, the SEQUENCE trial, directly compares the efficacy of ustekinumab (Stelara, Janssen) and risankizumab (Skyrizi, AbbVie) for moderate to severe Crohn’s disease (CD) in adults. All participants had unacceptable side effects or their disease was refractory to an anti–tumor necrosis factor therapy.
Ustekinumab blocks interleukin-12 (IL-12) and IL-23, whereas risankizumab only inhibits IL-23. They are both effective and safe medications. In the SEQUENCE trial, risankizumab induced greater endoscopic remission by week 48.
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The other study, the SPICY trial, explored whether changes in surgical techniques can improve outcomes, namely prevention of postoperative recurrence, in people with CD. For some people with CD, the mesentery can become a site of inflammation, and previous research suggests that removing the mesentery could be beneficial. The SPICY trial was a well-done, prospective study that explored whether removing the mesentery during a terminal ileum resection, rather than sparing it, as is now the standard of practice, reduced endoscopic CD recurrence. The bottom line is that it didn’t. Taking the extra effort to remove the mesentery did not lower endoscopic recurrence, so the study authors recommended continuing the standard mesentery-sparing approach.
The study is important, even if it is not practice changing, as a marker of ongoing interest in innovative surgical techniques for CD. In addition to studying mesentery removal, surgeons are studying whether Kono-S anastomosis and other surgical approaches result in a long-term improvement in CD outcomes. We await the data, and this is certainly a topic of future interest for The Regueiro Report.
Comparing IL Inhibitors
N Engl J Med 2024;391(3):213-223
This study included adults (age, 18-80 years) with moderate to severe CD, 230 who received standard doses of risankizumab at set intervals for 48 weeks and 193 who received ustekinumab on a set schedule. The participants completed all assigned treatments.
To be defined as having moderate to severe CD, patients needed a score of 220 to 450 on the Crohn’s Disease Activity Index (CDAI) and at least four daily soft or liquid stools according to the Bristol Stool Chart or a mean score of at least 2 on the daily abdominal pain scale, or both.
The investigators first compared clinical remission between the two medications at week 24, measured as a CDAI score of less than 150. This was a noninferiority analysis conducted on the first 50% of patients who completed their week 24 visit, with a noninferiority margin of 10 percentage points.
Risankizumab was found to be noninferior to ustekinumab in inducing clinical remission (risankizumab, 58.6% vs. ustekinumab, 39.5%; adjusted difference, 18.4 percentage points; 95% CI, 6.6-30.3).
At week 48, the investigators measured endoscopic remission, defined as a maximum of 4 on the Simple Endoscopic Score for Crohn’s Disease, with a decrease of at least 2 points from baseline and no subscore greater than 1. Risankizumab had stronger results in this area as well (risankizumab, 31.8% vs. ustekinumab, 16.2%; adjusted difference, 15.6 percentage points; 95% CI, 8.4 to 22.9; P<0.001).
The incidence of adverse events was similar in both groups.
Sparing the Mesentery
Lancet Gastroenterol Hepatol 2024;9(9):793-801
Of 131 adults (age =16 years) with CD who underwent a terminal ileal resection with anastomosis, 66 received extended mesenteric resection (experimental arm) and 65 had the standard mesenteric-sparing surgery (control arm). Six months after surgery, rates of endoscopic recurrence were similar in both groups, suggesting no additional benefit from mesenteric resection.
Similar numbers of patients demonstrated endoscopic recurrence in the extended mesenteric resection arm and the mesentery-sparing arm (42% vs. 43%, respectively; relative risk, 0.985; 95% CI, 0.663-1.464; P=1.0). In addition, there were higher incidences of anastomotic leakage and postoperative complications in the mesenteric resection group.
The authors concluded that the “data support the guideline-recommended mesenteric-sparing approach.”
This article is from the October 2024 print issue.