Takeda: VERDICT—ENTYVIO treat-to-target disease clearance delays first UC complication
- VERDICT randomized 672 adults with moderate–severe UC to three corticosteroid-free targets using vedolizumab-based treatment algorithms.
- About 400/672 (≈60%) of randomized patients met their assigned CSF target by Week 48; 52.1% in the disease-clearance arm (Group 3) reached target by Week 48.
- Disease clearance (Group 3) versus symptomatic remission (Group 1) prolonged time to first UC-related complication (HR 0.33; 95% CI 0.17–0.67; P=0.0014), reducing complication risk by ~70% up to 80 weeks after target achievement.
- Adverse event rates were similar across groups, with no new safety signals through 96 weeks.
Trial design
VERDICT (Phase 4, NCT04259138) randomized 672 adults with moderate to severe ulcerative colitis to three corticosteroid-free (CSF) treat-to-target arms using ENTYVIO-based escalation algorithms: Group 1 CSF symptomatic remission; Group 2 CSF symptomatic plus endoscopic remission; Group 3 CSF symptomatic, endoscopic and histologic remission (disease clearance). Targets were assessed at Weeks 16, 32 and 48. The primary outcome compared time to first UC-related complication up to 80 weeks after target achievement between Groups 3 and 1.
Key efficacy findings
Nearly 60% (400/672) of randomized patients achieved their assigned CSF target by Week 48 (Group 1: 137 [74.1%]; Group 2: 125 [56.3%]; Group 3: 138 [52.1%]). Among patients who reached assigned targets, more than half (57%) achieved disease clearance by Week 16. The primary endpoint was met: disease clearance (Group 3) prolonged time to first UC-related complication versus symptomatic remission (HR 0.33; 95% CI 0.17–0.67; P=0.0014), a ~70% reduction in complication risk up to 80 weeks after target achievement. Time to complication was similar between Groups 2 and 3 (HR 1.10; 95% CI 0.45–2.69; P=0.8023). Fifty-one UC-related complications occurred, with rescue therapy the most frequent.
Safety
The safety profile through 96 weeks was consistent with prior ENTYVIO data and showed no new safety signals. Adverse event rates were similar across groups and were not increased by treatment escalation or more frequent dosing. The most common events (≥5%) included ulcerative colitis, anaemia, haematochezia, COVID-19, influenza, nasopharyngitis and arthralgia.
Molecular analyses and implications
Exploratory proteomic and transcriptomic analyses in largely bio-naïve patients who achieved early disease clearance (Week 16) identified pathway changes linked to inflammation, mucosal homeostasis and tissue repair, suggesting biological signatures of deep healing that warrant further study. The trial provides prospective evidence that a treat-to-target strategy aiming for disease clearance with vedolizumab can alter the short- to mid-term course of UC.
Source: Takeda