CATEGORY: GUT & DIGESTIVE HEALTH
In the first head-to-head randomized trial of two modern biologic drugs for Crohn’s disease, risankizumab healed the intestinal lining in 31.8% of patients at one year versus 16.2% on ustekinumab—an adjusted difference of 15.6 percentage points—while proving no worse on symptom relief, with 58.6% versus 39.5% reaching clinical remission at 24 weeks.1
One Disease, Two Different Immune Targets
Crohn’s disease is a chronic condition in which the immune system attacks the lining of the digestive tract, producing pain, diarrhea, weight loss and, over time, lasting bowel damage. Both drugs in this trial are biologics—injectable medicines built from antibodies that intercept specific immune signals. Ustekinumab, the older of the two, blocks two signaling proteins at once (interleukin-12 and interleukin-23); risankizumab blocks interleukin-23 alone, a narrower aim at the signal most tied to gut inflammation. Every participant had already tried an anti-TNF drug—the earlier generation of biologics—without enough benefit or with side effects, so the trial answers the question patients actually face at that point: which drug next?
Judged by Symptoms at Twenty-Four Weeks, by Camera at Forty-Eight
The SEQUENCE trial randomly assigned 520 adults with moderate-to-severe Crohn’s disease to one drug or the other at standard doses for 48 weeks. Patients and doctors knew which drug was given, but the outcomes were scored by assessors kept unaware of the assignment—a design that preserves objectivity where full blinding is impractical. The trial set two bars in sequence, and its ambitions were built into that order: first, show risankizumab was at least no worse at bringing symptoms into remission by week 24; then, only if that held, test whether it was actually superior at endoscopic remission by week 48. Both bars were cleared.
Why Doctors Look Past Symptoms to the Lining Itself
Endoscopic remission means that when a camera examines the intestine, the lining looks largely healed—minimal ulcers or inflammation. It is a stricter standard than feeling better, because Crohn’s can smolder like embers under quiet ash: symptoms fade while inflammation quietly continues damaging the bowel. That is why specialists increasingly treat visible healing, not just comfort, as the goal. On that stricter standard the two drugs separated clearly—31.8% versus 16.2%—and the gap echoed in how patients fared overall: 90.2% of the risankizumab group completed the full course of treatment, compared with 72.8% on ustekinumab.
Similar Safety, and Who Paid for the Race
Side effects were similar in the two groups over the 48 weeks. The trial was funded by AbbVie, the maker of risankizumab, which is worth knowing alongside the design safeguard that matters most here: the disease scoring that produced these results was done by evaluators blinded to treatment. For the large group of people with Crohn’s disease who need a next option after anti-TNF therapy, this is the first randomized evidence directly comparing two of the leading candidates—and it found a real difference in how often the gut itself heals.
Key Takeaways
- In the first head-to-head trial of these two biologics, risankizumab matched ustekinumab on symptom remission and beat it on healing of the intestinal lining—31.8% versus 16.2% at 48 weeks.
- All 520 participants had already had an inadequate result with anti-TNF therapy, so the finding applies to that common second-line situation.
- Side-effect rates were similar, and more patients completed treatment on risankizumab (90.2% versus 72.8%).
- The trial was funded by risankizumab’s manufacturer; its endpoints were scored by doctors unaware of which drug each patient received.
References
- Peyrin-Biroulet L, Chapman JC, Colombel JF, et al. Risankizumab versus Ustekinumab for Moderate-to-Severe Crohn’s Disease. N Engl J Med. 2024;391(3):213–223. link