RELIEVE UCCD (CD)CD · Induction and maintenance
Efficacy and safety of duvakitug in patients with Crohn's disease (RELIEVE UCCD): a phase 2b, randomised, placebo-controlled trial
Jairath V, et al.
Lancet Gastroenterol Hepatol 2026 · PMID 42462749 (PubMed, opens in a new tab) · doi 10.1016/S2468-1253(26)00119-6 (full paper, opens in a new tab)
| Endpoint | Duvakitug 450 mg | Duvakitug 900 mg | Placebo | Difference |
|---|---|---|---|---|
| Endoscopic response, Week 14 (primary endpoint) | 26% (12/46) | 48% (22/46) | 13% (6/46) | Posterior mean difference vs placebo: 450 mg 13% (95% credible interval −3 to 29); 900 mg 33% (16 to 50) |
Source: Jairath 2026, abstract (modified intention to treat). Differences are Bayesian posterior means with 95% credible intervals; posterior probabilities of superiority were 0.94 (450 mg) and >0.99 (900 mg), against a success threshold of 0.90.
Structured abstract
BackgroundTL1A, a TNF-family cytokine, was a new therapeutic target in IBD. Duvakitug, an anti-TL1A antibody, needed placebo-controlled, dose-ranging evidence with an endoscopic endpoint in Crohn's disease.
MethodsPhase 2b, multicentre, randomised (1:1:1), placebo-controlled trial with a Bayesian primary analysis. 139 patients. Primary endpoint: Endoscopic response (≥50% reduction in SES-CD) at week 14; a dose succeeded if the posterior probability of exceeding placebo was ≥0.90.
ResultsPrimary result. 26% (12/46) with 450 mg and 48% (22/46) with 900 mg vs 13% (6/46) with placebo; posterior mean differences 13% (95% credible interval −3 to 29) and 33% (95% CrI 16 to 50); posterior probabilities of superiority 0.94 and >0.99
Take-homeDuvakitug, 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.
| Patients | 139 |
|---|---|
| Population | Adults aged 18–75 with moderately to severely active Crohn's disease, including inadequate response, loss of response or intolerance to previous therapies; 57% had prior exposure to at least one advanced therapy |
| Comparison | Duvakitug SC 2250 mg loading dose, then 450 mg or 900 mg every 2 weeks, vs placebo |
| Drugs | duvakitug |
| Classes | Anti-TL1A |
| Published | Jairath V, et al. Lancet Gastroenterol Hepatol 2026;11:786–96. |
Key points
- Both doses met the prespecified Bayesian success threshold; the 900 mg dose gave the larger effect.
- Adverse events: 67% (450 mg) and 43% (900 mg) vs 48% (placebo).
- Serious adverse events: 13% (450 mg) and 2% (900 mg) vs 11% (placebo).
- The UC cohort of RELIEVE UCCD was published separately (PMID 42462750).
Limitations
- Small phase 2b trial with a 14-week endpoint.
- Bayesian analysis with a 0.90 success threshold is less stringent than a conventional significance test; the 450 mg credible interval crossed zero.
- 95% of participants were White.
Commentary
Context. This is the first randomised, placebo-controlled anti-TL1A trial in Crohn’s disease with an endoscopic primary endpoint. The UC cohort is summarised in RELIEVE UCCD (UC).
Other anti-TL1A data in Crohn’s disease. In APOLLO-CD, an open-label, single-arm phase 2a trial of IV tulisokibart, endoscopic response at week 12 was 26.0% (13/50; 95% CI 15.9–39.6) in the per-protocol set (Feagan BG, et al. Lancet Gastroenterol Hepatol 2025;10:715–25; PMID 40456235). Without a placebo arm that figure cannot be compared directly with this trial.
Status. Interest in TL1A comes partly from its possible anti-fibrotic effect, which is unproven in people. As of October 2026, duvakitug was not approved in Canada and phase 3 trials were needed.
Journal club
Design
Phase 2b, multicentre, randomised (1:1:1), placebo-controlled trial with a Bayesian primary analysis. 139 patients.
Primary result. 26% (12/46) with 450 mg and 48% (22/46) with 900 mg vs 13% (6/46) with placebo; posterior mean differences 13% (95% credible interval −3 to 29) and 33% (95% CrI 16 to 50); posterior probabilities of superiority 0.94 and >0.99
Validity and applicability
- Small phase 2b trial with a 14-week endpoint.
- Bayesian analysis with a 0.90 success threshold is less stringent than a conventional significance test; the 450 mg credible interval crossed zero.
- 95% of participants were White.
Where it sits now
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.
- 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.
- DIVERSITY (2025): Filgotinib failed its week-10 induction endpoints in Crohn's disease, unlike upadacitinib in its own phase 3 trials, so JAK inhibitors should not be assumed to work equally well in Crohn's disease.
- GALAXI-2 and GALAXI-3 (2025): IV guselkumab induction followed by SC maintenance is effective in Crohn's disease and outperformed ustekinumab at week 48 on several endpoints.
- GRAVITI (2025): Guselkumab can be given entirely by subcutaneous injection for both induction and maintenance in Crohn's disease, with no IV infusion needed.
Questions for discussion
- Success was defined as a posterior probability of at least 0.90. How does that compare with a conventional P<0.05 test, and what does it mean for the 450 mg dose?
- Adverse events were more frequent with 450 mg than with 900 mg. How do you interpret a safety pattern that does not follow dose?
- What would you want phase 3 to show before using an anti-TL1A antibody instead of an established advanced therapy?