ARTEMIS-UCUC · Induction and maintenance
Phase 2 Trial of Anti-TL1A Monoclonal Antibody Tulisokibart for Ulcerative Colitis
Sands BE, et al.
N Engl J Med 2024 · PMID 39321363 (PubMed, opens in a new tab) · doi 10.1056/NEJMoa2314076 (full paper, opens in a new tab)
| Endpoint | Tulisokibart | Placebo | Difference |
|---|---|---|---|
| Clinical remission, Week 12 · cohort 1, all patients (135) (primary endpoint) | 26% | 1% | +25 points (95% CI 14–37); P<0.001 |
| Clinical remission, Week 12 · test-positive patients (75) | 32% | 11% | +21 points (95% CI 2–38); P=0.02 |
The 1% placebo rate inflates the difference, and test-positive patients did not show a clearly larger effect than the whole cohort.
Source: Sands 2024, abstract. The abstract gives no per-arm counts.
Structured abstract
BackgroundTL1A, a TNF-family cytokine linked to intestinal inflammation and fibrosis, was a new target in UC; a genetic-based test was designed to identify likely responders.
MethodsPhase 2, randomised, double-blind, placebo-controlled 12-week induction trial with a genetic-based companion diagnostic. 178 patients. Primary endpoint: Clinical remission at week 12 (cohort 1).
ResultsPrimary result. 26% vs 1%; difference 25 percentage points (95% CI 14–37); P<0.001
Take-homeAnti-TL1A therapy is a new mechanism in UC; tulisokibart produced a large placebo-adjusted remission rate in a short phase 2 trial, with phase 3 results still awaited.
| Patients | 178 |
|---|---|
| Population | Moderately to severely active UC with glucocorticoid dependence or failure of conventional or advanced therapy. Cohort 1 (135) enrolled regardless of the diagnostic test; cohort 2 (43) enrolled test-positive patients only. |
| Comparison | Tulisokibart IV 1000 mg on day 1, then 500 mg at weeks 2, 6 and 10, vs placebo |
| Drugs | tulisokibart |
| Classes | Anti-TL1A |
| Published | Sands BE, et al. N Engl J Med 2024;391:1119–29. |
Key points
- Test-positive patients (cohorts 1 and 2 combined, n=75): remission 32% vs 11%; difference 21 points (95% CI 2–38); P=0.02.
- The test-positive subgroup did not show a clearly larger effect than the whole cohort, so the value of the companion diagnostic is unproven.
- Adverse events were similar with tulisokibart and placebo; most were mild to moderate.
- TL1A is a TNF-family cytokine linked to both inflammation and fibrosis, a new target in IBD.
Limitations
- Phase 2, 12 weeks only; no maintenance data in this paper.
- An unusually low placebo remission rate (1%) inflates the treatment difference.
- Small sample.
Commentary
Context. Three anti-TL1A antibodies have published phase 2 UC data: tulisokibart (this trial), afimkibart (TUSCANY-2, PMID 40706613) and duvakitug (RELIEVE UCCD, PMID 42462750). Interest in the class comes partly from its possible anti-fibrotic effect, which matters more for stricturing Crohn’s disease.
Crohn’s disease. In the open-label, single-arm APOLLO-CD phase 2a trial, IV tulisokibart gave a week-12 endoscopic response of 26.0% (13/50) (PMID 40456235). Randomised phase 2b data in Crohn’s disease are available for duvakitug (RELIEVE UCCD (CD)).
Status. As of October 2026, phase 3 UC trials of anti-TL1A antibodies were ongoing and none was approved in Canada.
Journal club
Design
Phase 2, randomised, double-blind, placebo-controlled 12-week induction trial with a genetic-based companion diagnostic. 178 patients.
Primary result. 26% vs 1%; difference 25 percentage points (95% CI 14–37); P<0.001
Validity and applicability
- Phase 2, 12 weeks only; no maintenance data in this paper.
- An unusually low placebo remission rate (1%) inflates the treatment difference.
- Small sample.
Where it sits now
Anti-TL1A therapy is a new mechanism in UC; tulisokibart produced a large placebo-adjusted remission rate in a short phase 2 trial, with phase 3 results still awaited.
- RELIEVE UCCD (CD) (2026): Duvakitug, an anti-TL1A antibody, gave a dose-related endoscopic response signal in Crohn's disease in phase 2b; phase 3 trials will decide whether TL1A becomes a new Crohn's disease target.
- ASTRO (2026): Guselkumab can be started with subcutaneous 400 mg injections instead of IV infusions, with clear benefit over placebo by week 12.
- RELIEVE UCCD (UC) (2026): Duvakitug, an anti-TL1A antibody, showed a dose-related remission signal in UC in phase 2b; phase 3 trials will decide its place.
- QUASAR (2025): Guselkumab induces and maintains remission in UC, and the follow-up ASTRO trial showed induction can be given subcutaneously.
Questions for discussion
- Placebo remission was 1%, far below most UC trials. How does an unusually low placebo rate distort a treatment difference, and what might explain it here?
- The companion diagnostic was meant to enrich for responders. What result would you need before using a test like this to choose therapy?
- This was a 12-week phase 2 trial. What would you want from phase 3 before using an anti-TL1A antibody?