STARDUSTCD · Treatment strategy
Treat to target versus standard of care for patients with Crohn's disease treated with ustekinumab (STARDUST): an open-label, multicentre, randomised phase 3b trial
Danese S, et al.
Lancet Gastroenterol Hepatol 2022 · PMID 35120656 (PubMed, opens in a new tab) · doi 10.1016/S2468-1253(21)00474-X (full paper, opens in a new tab)
| Endpoint | Treat to target | Standard of care | Difference |
|---|---|---|---|
| Endoscopic response, SES-CD down ≥50% (primary endpoint) | 38% (83/219) | 30% (66/221) | P=0.087 |
| Endoscopic remission | 11% (25/219) | 15% (32/221) | P=0.334 |
| Clinical remission | 62% (135/219) | 70% (154/221) | P=0.072 |
| Clinical response | 68% (149/219) | 78% (172/221) | P=0.020 |
No endpoint significantly favoured treat to target, and clinical response was significantly lower with it.
Source: Danese 2022, abstract.
Structured abstract
BackgroundTreat to target, with early endoscopy, biomarkers and dose escalation for persistent inflammation, was widely advocated in Crohn's disease but had not been tested with ustekinumab against symptom-driven care.
MethodsOpen-label, multicentre, randomised phase 3b trial; randomisation at week 16 after open-label induction. 440 patients. Primary endpoint: Endoscopic response at week 48 (≥50% decrease in SES-CD from baseline), non-responder imputation.
ResultsPrimary result. 38% (83/219) with treat-to-target vs 30% (66/221) with standard of care; P=0.087 (not significant).
Take-homeWith ustekinumab, an endoscopy-driven treat-to-target algorithm did not improve 48-week endoscopic response over clinically driven care; treat-to-target only helps if escalation has something to add.
| Patients | 440 |
|---|---|
| Population | Adults with moderate-to-severe Crohn's disease (CDAI 220–450, SES-CD ≥3) who had failed conventional therapy and/or one biologic. 498 received ustekinumab induction; those with a CDAI improvement of ≥70 points at week 16 were randomised. |
| Comparison | Treat-to-target vs standard-of-care ustekinumab maintenance |
| Drugs | ustekinumab |
| Classes | Anti-IL-12/23 |
| Published | Danese S, et al. Lancet Gastroenterol Hepatol 2022;7:294–306. |
Key points
- Treat-to-target: every 12 or 8 weeks by SES-CD improvement at week 16, escalating to every 4 weeks if targets were missed. Standard of care: every 12 or 8 weeks, with escalation per European labelling.
- Endoscopic remission 11% vs 15% (P=0.334); mucosal healing 14% vs 17% (P=0.449).
- Clinical remission 62% vs 70% (P=0.072); clinical response was lower with treat-to-target (68% vs 78%; P=0.020).
- Adverse events were similar (for example nasopharyngitis 13% in each arm).
- Intestinal ultrasound substudy (77 patients): ultrasound response could be seen by week 4, and by week 48 ultrasound response was 46.3% and transmural remission 24.1% (PMID 35842121).
Limitations
- Open-label; the standard-of-care arm could also escalate, narrowing the contrast between arms.
- Escalation options were limited to shorter ustekinumab intervals, which may add little (see REScUE).
- Only patients with a clinical response at week 16 were randomised.
- Industry funded (Janssen-Cilag).
Commentary
STARDUST is the counterweight to CALM. A treat-to-target strategy is only as good as the escalation step it triggers. When the only option is to shorten the interval of the same drug, tighter monitoring may not change outcomes, and switching therapy may be the more useful response to a missed target.
Its intestinal ultrasound substudy is one of the first multicentre interventional datasets showing that ultrasound can track early response, which supports point-of-care ultrasound for monitoring.
Journal club
Design
Open-label, multicentre, randomised phase 3b trial; randomisation at week 16 after open-label induction. 440 patients.
Primary result. 38% (83/219) with treat-to-target vs 30% (66/221) with standard of care; P=0.087 (not significant).
Validity and applicability
- Open-label; the standard-of-care arm could also escalate, narrowing the contrast between arms.
- Escalation options were limited to shorter ustekinumab intervals, which may add little (see REScUE).
- Only patients with a clinical response at week 16 were randomised.
- Industry funded (Janssen-Cilag).
Where it sits now
With ustekinumab, an endoscopy-driven treat-to-target algorithm did not improve 48-week endoscopic response over clinically driven care; treat-to-target only helps if escalation has something to add.
- CALM (2017): Escalating therapy on biomarkers plus symptoms, rather than symptoms alone, gives more mucosal healing in early Crohn's disease.
- PROFILE (2024): In newly diagnosed active Crohn's disease, starting infliximab plus an immunomodulator straight away gives far better 1-year and 5-year outcomes than step-up care.
- STRIDENT (2022): Symptomatic Crohn's strictures with active inflammation often respond to adalimumab; intensifying therapy did not significantly improve symptoms; secondary results on treatment failure and MRI stricture appearance favoured it but are hypothesis-generating.
- REACT (2015): Early combined immunosuppression did not improve 1-year symptom remission but lowered 2-year surgery, admissions and complications, supporting early effective therapy.
Questions for discussion
- Clinical response was lower with treat to target. How could a more intensive strategy leave patients doing worse on symptoms?
- Escalation could only shorten the ustekinumab interval. When does treat to target fail because there is little to escalate to, rather than because the strategy is wrong?
- Compare STARDUST with CALM. Which design differences might explain why one strategy trial was positive and the other was not?