RELIEVE UCCD (UC)UC · Induction and maintenance
Efficacy and safety of duvakitug in patients with ulcerative colitis (RELIEVE UCCD): a phase 2b, randomised, placebo-controlled trial
Reinisch W, et al.
Lancet Gastroenterol Hepatol 2026 · PMID 42462750 (PubMed, opens in a new tab) · doi 10.1016/S2468-1253(26)00120-2 (full paper, opens in a new tab)
| Endpoint | Duvakitug 450 mg | Duvakitug 900 mg | Placebo | Difference |
|---|---|---|---|---|
| Clinical remission, Week 14 · modified Mayo score (primary endpoint) | 36% (17/47) | 48% (22/46) | 20% (9/44) | Posterior mean difference vs placebo: 450 mg 15% (95% credible interval −3 to 33); 900 mg 26% (8 to 44) |
Source: Reinisch 2026, abstract (modified intention to treat). Differences are Bayesian posterior means with 95% credible intervals; posterior probabilities of superiority were 0.95 (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 in moderately to severely active UC.
MethodsPhase 2b, multicentre, randomised (1:1:1), placebo-controlled trial with a Bayesian primary analysis. 137 patients. Primary endpoint: Clinical remission by modified Mayo score at week 14; a dose succeeded if the posterior probability of exceeding placebo was ≥0.90.
ResultsPrimary result. 36% (17/47) with 450 mg and 48% (22/46) with 900 mg vs 20% (9/44) with placebo; posterior mean differences 15% (95% credible interval −3 to 33) and 26% (95% CrI 8 to 44); posterior probabilities of superiority 0.95 and >0.99
Take-homeDuvakitug, an anti-TL1A antibody, showed a dose-related remission signal in UC in phase 2b; phase 3 trials will decide its place.
| Patients | 137 |
|---|---|
| Population | Adults aged 18–75 with moderately to severely active UC, including inadequate response, loss of response or intolerance to conventional or advanced therapy; 31% had prior exposure to an approved 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 | Reinisch W, et al. Lancet Gastroenterol Hepatol 2026;11:775–85. |
Key points
- Both doses met the prespecified Bayesian success threshold; the 900 mg dose gave the larger effect.
- Adverse events: 49% (450 mg) and 43% (900 mg) vs 52% (placebo).
- One serious adverse event in each of the 900 mg (non-infective oophoritis) and placebo (intracranial haemorrhage) groups.
- The Crohn's disease cohort of RELIEVE UCCD was published separately (PMID 42462749).
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.
- Only 31% had previous exposure to an approved advanced therapy.
Commentary
Context. Duvakitug is the third anti-TL1A antibody with published phase 2 UC data, after tulisokibart (ARTEMIS-UC, PMID 39321363) and afimkibart (TUSCANY-2, PMID 40706613). It is not approved in Canada. The Crohn’s disease cohort is summarised in RELIEVE UCCD (CD).
Journal club
Design
Phase 2b, multicentre, randomised (1:1:1), placebo-controlled trial with a Bayesian primary analysis. 137 patients.
Primary result. 36% (17/47) with 450 mg and 48% (22/46) with 900 mg vs 20% (9/44) with placebo; posterior mean differences 15% (95% credible interval −3 to 33) and 26% (95% CrI 8 to 44); posterior probabilities of superiority 0.95 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.
- Only 31% had previous exposure to an approved advanced therapy.
Where it sits now
Duvakitug, an anti-TL1A antibody, showed a dose-related remission signal in UC in phase 2b; phase 3 trials will decide its place.
- 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.
- QUASAR (2025): Guselkumab induces and maintains remission in UC, and the follow-up ASTRO trial showed induction can be given subcutaneously.
- TUSCANY-2 (2025): Afimkibart missed its phase 2b primary endpoint (total Mayo remission), although remission by the modified Mayo score favoured it; anti-TL1A therapy still needs phase 3 proof.
Questions for discussion
- The 450 mg credible interval crossed zero, yet the dose met the success threshold. How would you explain that to a colleague?
- Most patients were naive to advanced therapy. How might the results differ in patients who have failed several advanced therapies?
- Several anti-TL1A antibodies are in development. What would you want phase 3 trials to show to tell them apart?