REScUECD · Biosimilars and dosing
The Effect of Dose Intensification After Secondary Loss of Response to Ustekinumab in Crohn's Disease: Results of the REScUE Study
Bossuyt P, et al.
Gastroenterology 2026 · PMID 41747777 (PubMed, opens in a new tab) · doi 10.1053/j.gastro.2026.01.042 (full paper, opens in a new tab)
| Endpoint | Every 4 weeks | Every 8 weeks | Difference |
|---|---|---|---|
| Steroid-free clinical remission, Week 48 · PRO2 remission, calprotectin below 250 µg/g, no steroids (primary endpoint) | 15% | 19% | Difference 4%; P=0.5 |
| Serious adverse events, Lower is better | 17% | 13% |
Both arms had IV reinduction, so the trial tests the dosing interval, not reinduction itself.
Source: Bossuyt 2026, abstract (108 randomised). The abstract gives percentages only, without counts or confidence intervals.
Structured abstract
BackgroundSecondary loss of response to ustekinumab occurs in Crohn's disease, and several dose-intensification regimens were in use without a prospective randomised comparison.
MethodsInvestigator-initiated, multicentre, randomised, placebo-controlled trial (15 hospitals in Belgium). 108 patients. Primary endpoint: Steroid-free clinical remission at week 48: PRO2 remission (abdominal pain ≤1 and stool frequency ≤3), faecal calprotectin below 250 µg/g, and no steroids in the 90 days before week 48.
ResultsPrimary result. 15% (every 4 weeks) vs 19% (every 8 weeks); difference 4%; P=0.5.
Take-homeAfter secondary loss of response to ustekinumab, IV reinduction plus every-4-week dosing is no better than reinduction plus every-8-week dosing, and few patients regain remission either way.
| Patients | 108 |
|---|---|
| Population | Adults with Crohn's disease on ustekinumab 90 mg SC every 8 weeks with secondary loss of response (PRO2: abdominal pain score above 1 and more than 3 liquid or very soft stools) and objective evidence of disease. |
| Comparison | A single IV ustekinumab reinduction (about 6 mg/kg), then 90 mg SC every 4 weeks vs every 8 weeks, until week 48 |
| Drugs | ustekinumab |
| Classes | Anti-IL-12/23 |
| Published | Bossuyt P, et al. Gastroenterology 2026;171:99–109. |
Key points
- Shortening the interval to every 4 weeks after IV reinduction was not better than continuing every 8 weeks.
- Serious adverse events: 17% vs 13%.
- Remission rates were low in both arms, so dose intensification rarely rescues secondary loss of response to ustekinumab.
Limitations
- No arm without IV reinduction, so the effect of reinduction itself cannot be judged.
- Moderate sample size from one country.
- Strict composite primary endpoint including calprotectin and steroid-free status.
Commentary
REScUE is one of the few randomised trials of dose escalation for loss of response. It argues against relying on interval shortening of ustekinumab and in favour of an early switch. After anti-TNF exposure, SEQUENCE supports an IL-23 p19 inhibitor. Check for objective inflammation and other causes of symptoms (strictures, bile acid diarrhea, infection) before changing therapy.
Journal club
Design
Investigator-initiated, multicentre, randomised, placebo-controlled trial (15 hospitals in Belgium). 108 patients.
Primary result. 15% (every 4 weeks) vs 19% (every 8 weeks); difference 4%; P=0.5.
Validity and applicability
- No arm without IV reinduction, so the effect of reinduction itself cannot be judged.
- Moderate sample size from one country.
- Strict composite primary endpoint including calprotectin and steroid-free status.
Where it sits now
After secondary loss of response to ustekinumab, IV reinduction plus every-4-week dosing is no better than reinduction plus every-8-week dosing, and few patients regain remission either way.
- SEQUENCE (2024): After anti-TNF failure, risankizumab beats ustekinumab for endoscopic remission, so an IL-23 p19 inhibitor is the stronger second-line choice of the two.
- LIBERTY-CD (2024): After IV infliximab induction, subcutaneous infliximab 120 mg every 2 weeks maintains remission and endoscopic response in Crohn's disease, an option for patients who prefer injections to infusions.
- SERENE-CD (2022): Extra-intensive adalimumab induction does not beat the standard 160/80 mg regimen, and proactive TDM-guided maintenance was no better than dosing adjusted to symptoms and CRP.
- VISIBLE 2 (2022): After two IV doses, vedolizumab 108 mg SC every 2 weeks maintains remission in Crohn's disease better than placebo, so patients can switch to home injections.
Questions for discussion
- Both arms received IV reinduction. What question would a third arm without reinduction have answered?
- The primary endpoint required PRO2 remission, a calprotectin below 250 µg/g and no steroids. How does a strict composite affect the chance of showing a difference?
- After secondary loss of response to ustekinumab, when would you intensify and when would you switch class?