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Duvakitug 900 mg Achieves Clinical Remission in Nearly Half of Ulcerative Colitis Patients at 14 Weeks
In a phase 2b randomised trial, 48% of patients receiving duvakitug 900 mg achieved clinical remission at week 14, compared with 20% on placebo — a posterior mean difference of 26% (95% CrI 8 to 44) with a greater than 99% posterior probability of superiority. The 450 mg dose also surpassed the prespecified efficacy threshold, though with a credible interval that included zero, making its benefit somewhat less certain.
What Was Studied
The trial investigated whether duvakitug — a monoclonal antibody targeting TNF-like cytokine 1A (TL1A) — could induce clinical remission in adults with moderately to severely active ulcerative colitis. The primary outcome was clinical remission assessed by modified Mayo score at week 14, evaluated across two doses to identify a dose-response signal for this novel mechanism of action.
How It Was Studied
This multicentre, placebo-controlled, phase 2b randomised trial enrolled 137 adults aged 18 to 75 years with moderately to severely active ulcerative colitis, including patients who had experienced inadequate response, loss of response, or intolerance to conventional or advanced therapies. Participants were assigned in a 1:1:1 ratio to receive a subcutaneous loading dose of 2250 mg duvakitug followed by either 450 mg (n=47) or 900 mg (n=46) every two weeks, or to matching placebo (n=44). Efficacy was assessed at week 14 using a Bayesian analytical framework, in which a dose was declared successful if the posterior probability of superiority over placebo reached 0.90 or greater. The study population had a mean age of 41 years, was predominantly male (63%) and White (96%), and approximately 31% had prior exposure to an approved advanced therapy.
What Was Observed
- Clinical remission — 900 mg dose: Nearly half of patients on duvakitug 900 mg achieved clinical remission at week 14 (48%, 22 of 46), compared with 20% on placebo (9 of 44). The posterior mean difference was approximately 26 percentage points higher than placebo (95% CrI 8 to 44), and the posterior probability of superiority exceeded 0.99 — well above the prespecified 0.90 threshold.
- Clinical remission — 450 mg dose: The lower dose also showed improvement over placebo, with 36% of patients (17 of 47) achieving remission versus 20% in the placebo group. The posterior mean difference was 15% (95% CrI −3 to 33), and the posterior probability of superiority reached 0.95, meeting the efficacy threshold — though the credible interval crossing zero introduces some uncertainty about the magnitude of benefit.
- Safety profile: Adverse event rates were comparable across all three groups — 49% in the 450 mg group, 43% in the 900 mg group, and 52% in the placebo group. The most frequently reported events were upper respiratory tract infection and anaemia, occurring at low frequencies across all arms. Serious adverse events were rare: one case of non-infective oophoritis occurred in the 900 mg group and one intracranial haemorrhage in the placebo group.
Why This Matters
Duvakitug represents a distinct mechanistic approach to treating ulcerative colitis by targeting TL1A, a cytokine pathway not addressed by currently approved therapies. These findings offer proof-of-concept that anti-TL1A therapy can produce clinically meaningful remission rates in a patient population that includes those who have already failed conventional or advanced treatments. The demonstration of a dose-response relationship and an acceptable short-term safety profile provides a scientific basis for advancing duvakitug into larger, longer-duration phase 3 trials.
How to Read This Result
While the 900 mg dose met its Bayesian efficacy threshold convincingly, the small overall sample size (N=137) and short 14-week follow-up limit the precision of both the efficacy and safety estimates, and these findings should be considered preliminary until confirmed in larger, longer-term trials.
Limitations
The trial enrolled only 137 participants across three arms, limiting the statistical precision of both efficacy and safety estimates. Just 31% of patients had prior exposure to an approved advanced therapy, which constrains how broadly the results apply to heavily pre-treated or biologic-experienced populations. The Bayesian analytical approach — while prespecified — may be less familiar than conventional frequentist hypothesis testing, potentially affecting how results are interpreted across audiences. Finally, the 14-week observation window provides no information about long-term durability of remission or the extended safety profile of duvakitug.