CATEGORY: GUT & DIGESTIVE HEALTH
Risankizumab healed the intestinal lining in 31.8% of Crohn’s patients at one year, against 16.2% on ustekinumab, an adjusted gap of 15.6 percentage points.1 It proved no worse on symptom relief either, with 58.6% against 39.5% reaching clinical remission at 24 weeks. This was the first head-to-head randomized trial of two modern biologic drugs for the disease.
Two Drugs, Two Aims at the Immune System
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 here 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 been through an anti-TNF drug, the earlier generation of biologics, without enough benefit or with side effects. So the trial answers the question those patients actually face: which drug next?
Symptoms at Twenty-Four Weeks, a Camera at Forty-Eight
The SEQUENCE trial sorted 520 adults with moderate-to-severe Crohn’s disease at random between the two medicines, at standard doses, for 48 weeks. Patients and doctors knew which drug was given. The outcomes, though, 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. 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 the Lining Matters More Than the Symptoms
Endoscopic remission means that when a camera examines the intestine, the lining looks largely healed, with minimal ulcers or inflammation. That is a stricter standard than feeling better. Crohn’s can smolder like embers under quiet ash, symptoms fading while inflammation keeps damaging the bowel. On the stricter standard the two drugs separated clearly, 31.8% against 16.2%, and the gap echoed in how patients fared overall: 90.2% of the risankizumab group completed the full course of treatment, against 72.8% on ustekinumab. Side effects were similar in the two groups across the 48 weeks. AbbVie, which makes risankizumab, funded the trial, and the disease scoring that produced these results was done by evaluators blinded to treatment.
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% against 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% against 72.8%.
- Risankizumab’s manufacturer funded the trial. 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