VERDICT Links Vedolizumab Disease Clearance to Fewer UC Complications

Patients with moderate to severe ulcerative colitis (UC) who achieved corticosteroid-free disease clearance with vedolizumab (Entyvio) had a significantly longer time to first UC-related complication than those who achieved symptomatic remission alone, according to results from the phase 4 VERDICT trial.¹

In the achieved-target population, disease clearance was associated with a 67% lower hazard of a first UC-related complication (HR, 0.33; 95% CI, 0.17–0.67; P = .0014). The findings were presented as late-breaking data at United European Gastroenterology (UEG) Week 2026 in Barcelona, Spain.¹

VERDICT is the first randomized trial in UC to prospectively evaluate disease clearance, defined as the combination of corticosteroid-free symptomatic, endoscopic, and histologic remission, as a prespecified treatment target.¹

“VERDICT suggests that implementation of a treat-to-target strategy can change the disease course,” Vipul Jairath, MBChB, DPhil, FRCP, FRCPC, professor of medicine at Western University, chief medical officer of Alimentiv, and lead study author, said in a statement from Takeda.¹

VERDICT Trial Design and Treatment Targets

VERDICT (NCT04259138) was a randomized phase 4 trial conducted by Alimentiv in collaboration with Takeda. The study enrolled 672 adults with active moderate to severe UC, defined by a Mayo rectal bleeding subscore ≥1 and Mayo endoscopic score ≥2. Most participants were biologic-naive and/or had severe endoscopic disease.¹˒²

Patients were randomized to 1 of 3 increasingly stringent corticosteroid-free treatment targets:

• Group 1: Symptomatic remission, defined as a Mayo rectal bleeding subscore of 0.
• Group 2: Symptomatic remission plus endoscopic remission, defined as a Mayo endoscopic score ≤1.
• Group 3: Symptomatic and endoscopic remission plus histologic remission, defined as a Geboes score <2B.0, collectively termed disease clearance.

The trial initially used a 2:3:5 randomization ratio across groups 1, 2, and 3. Following an interim analysis, the ratio was changed to 5:4:1 in May 2023 to help achieve approximately 100 patients reaching their assigned target in each group.²

Treatment targets were assessed at weeks 16, 32, and 48. Patients who did not achieve their assigned target underwent treatment escalation according to prespecified vedolizumab-based algorithms, including increased dosing frequency when indicated.¹˒²

The primary outcome compared time from target achievement to first UC-related complication between groups 3 and 1 over up to 80 weeks. Complications included hospitalization, colectomy, rescue therapy use, treatment-related events, and other UC-related complications.¹

Disease Clearance Associated With Fewer UC Complications

Of the 672 randomized patients, 400 (59.5%) achieved their assigned corticosteroid-free treatment target by week 48. Target achievement rates declined as treatment goals became more stringent.¹

Treatment TargetPatients Achieving TargetSymptomatic remission (group 1)137 (74.1%)Symptomatic plus endoscopic remission (group 2)125 (56.3%)Disease clearance (group 3)138 (52.1%)

Among patients who achieved their assigned targets, the disease-clearance group experienced a significantly longer time to first UC-related complication than the symptomatic-remission group (HR, 0.33; 95% CI, 0.17–0.67; P = .0014).¹

However, time to first complication did not differ significantly between patients achieving symptomatic plus endoscopic remission and those achieving disease clearance (HR, 1.10; 95% CI, 0.45–2.69; P = .8023). More than 80% of patients in group 2 who achieved their assigned target also achieved histologic remission at week 48.¹

Across the study, 51 UC-related complications were reported, with rescue therapy use representing the most frequent event.¹

These findings suggest that achieving deeper remission may be associated with improved clinical outcomes, although the absence of a significant difference between groups 2 and 3 leaves the additional benefit of explicitly targeting histologic remission beyond endoscopic remission uncertain.

Vedolizumab Safety Through 96 Weeks

Takeda reported similar adverse event rates across treatment groups, with no apparent increase associated with treatment escalation or more frequent vedolizumab dosing. The company stated that the safety profile through 96 weeks was generally consistent with previously reported vedolizumab data, with no new safety signals identified.¹

The most commonly reported adverse events, occurring in ≥5% of patients, included UC, anemia, hematochezia, COVID-19, influenza, nasopharyngitis, and arthralgia. Detailed adverse event rates by treatment group were not provided in the company's announcement.¹

What VERDICT Means for UC Treat-to-Target Strategies

Current treat-to-target recommendations in UC emphasize clinical remission and endoscopic healing, while histologic remission has generally been considered an additional measure of disease control rather than a formal treatment target.³

VERDICT adds prospective randomized evidence evaluating increasingly stringent treatment goals and their relationship with subsequent UC-related complications. However, the primary analysis focused on patients who achieved their assigned targets, rather than all randomized participants, and approximately 40% did not reach their assigned target by week 48.

The findings therefore should not be interpreted as establishing the same magnitude of benefit for all patients assigned to a disease-clearance strategy. Additionally, because more than 80% of patients achieving the symptomatic plus endoscopic target also achieved histologic remission, the incremental clinical benefit of specifically targeting histologic remission remains unresolved.

The trial evaluated vedolizumab-based treatment algorithms in a largely biologic-naive population, potentially limiting generalizability to patients with extensive prior advanced therapy exposure.

Although the findings support an association between achieving disease clearance and longer time to UC-related complications, additional analyses will be important to clarify whether pursuing histologic remission as a distinct treatment target provides benefits beyond those achieved with symptomatic and endoscopic remission.

References

1. First and only ulcerative colitis treat-to-target trial shows treating to disease clearance vs. symptomatic remission with ENTYVIO (vedolizumab) prolongs time to first disease-related complication. News release. Takeda. October 19, 2026. Accessed October 19, 2026. https://www.takeda.com/newsroom/newsreleases/2026/verdict-trial-disease-clearance/

2. Jairath V, Zou G, Wang Z, et al. Determining the optimal treatment target in patients with ulcerative colitis: rationale, design, protocol and interim analysis for the randomised controlled VERDICT trial. BMJ Open Gastroenterol. 2024;11(1). doi:10.1136/bmjgast-2023-001218

3. Turner D, Ricciuto A, Lewis A, et al. STRIDE-II: an update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative of the International Organization for the Study of IBD (IOIBD): determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology. 2021;160(5):1570-1583. doi:10.1053/j.gastro.2020.12.031