Duvakitug - Anti-TL1A Therapy in IBD: The Lancet Gastroenterology & Hepatology | August 2026

Introduction:

Despite an expanding range of advanced therapies for inflammatory bowel disease (IBD), many patients fail to achieve durable remission or lose response over time. TL1A is an attractive therapeutic target because it is implicated in both intestinal inflammation and fibrotic remodelling. The phase 2b RELIEVE UCCD trial evaluated duvakitug, an anti-TL1A monoclonal antibody, simultaneously in Crohn’s disease (CD) and ulcerative colitis (UC).

Why was this study needed?

Current therapies do not provide sustained disease control for many patients with moderate-to-severe IBD.

Persistent inflammation in CD can lead to progressive bowel damage and fibrosis.

TL1A inhibition potentially targets pathways involved in both inflammation and fibrosis.

The study importantly included both advanced therapy–naive and previously treated patients.

Results:

In Crohn’s disease, endoscopic response at week 14 occurred in 48% with duvakitug 900 mg vs 13% with placebo; response with 450 mg was 26%.

In ulcerative colitis, clinical remission occurred in 48% with 900 mg and 36% with 450 mg vs 20% with placebo.

Benefit was observed in both advanced therapy–experienced and therapy-naive patients, with a particularly encouraging signal for the 900-mg dose.

No new major safety signal emerged; common adverse events included anemia, nasopharyngitis, headache, and upper respiratory infections.

Clinical Impact:

The most interesting feature of TL1A inhibition is its potential to move beyond conventional inflammatory suppression toward disease modification, particularly if an effect on fibrosis can eventually be demonstrated. The strong endoscopic response in CD is therefore especially relevant.

However, this remains a relatively small 14-week phase 2b study. Whether these responses translate into durable endoscopic remission, reduced bowel damage, fewer strictures or surgery, and acceptable long-term safety requires phase 3 confirmation.

Bottom Line:

Duvakitug produced strong early efficacy in both Crohn’s disease and ulcerative colitis, including patients previously exposed to advanced therapies. Anti-TL1A therapy is emerging as one of the most promising new mechanistic classes in IBD—but durability, long-term safety, and true antifibrotic benefit remain the key questions for phase 3 trials.