What’s new in UC: UEGW ’24 and ECCO ‘25

DISEASE CLEARANCE, RESPONSE PREDICTION AND TREATMENT PERSISTENCE IN UC

Clinical studies on the effectiveness of therapies for UC often use endpoints that include clinical or endoscopic remission, but histological remission is also increasingly reported. Achieving the combination of these endpoints in one and the same patient is called disease clearance (DC)¹, but evidence on whether pursuing such strict treatment targets will result in a significant benefit to patients is currently lacking. In addition, it is important that patients can maintain their treatment outcomes for as long as possible.
During the past congresses, several abstracts were presented that are very relevant in the context of these questions. In this communication we would like to bring a selection of some abstracts in the spotlight.
 

Disease clearance in UC: main takeaways

• Interim results from the VERDICT trial show improvement in all endpoints between weeks 16, 32 and 482⁴

• VERDICT demonstrates that it is possible to achieve the stringent endpoinachieve the stringent endpoint of disease clearance (DC) in patients, although to a lesser extent than the simpler endpoint of pure corticosteroid-free symptomatic remission^2,4
• Post-hoc analysis of the mirikizumab LUCENT-UC trials³, as well as prospective⁵ and retrospective⁶ cohort studies support the concept of disease clearance  
  

UEGW 2024 brought us the interim results of clearance week 32 of the VERDICT randomized controlled trial², and ECCO 2025 added the interim results of week 48⁴ . The VERDICT trial investigates whether applying the stricter treatment target of DC leads to a more favorable outcome week for UC patients. 

Patients were randomized into three groups (see Fig 1), with each group having to meet increasingly strict treatment targets. The three arms and their respective treatment targets were defined as follows: 1) CSF symptomatic remission (Mayo rectal bleeding subscore = 0), 2) CSF symptomatic remission and endoscopic remission (Mayo Endoscopic Score [MES]≤1), and 3) CSF symptomatic remission and endoscopic remission and histologic remission (Geboes score<2B.0). In the patients who reached their week 32 or week 48 visit, the proportion of patients in the three groups who achieve remission is as follows (Figure 2).

This interim analysis of the as observed data shows that the strict target of CS-free symptomatic and endoscopic and histological remission was achieved in 70.1% of the bio-naïve patients, and 50% of the bio-experienced patients who had reached their week 48 visit.

After the completion of the VERDICT study, which will run for a total of two years, it will become clear to what extent patients benefit from the use of such stricter treatment targets.

Although it has not been formally demonstrated that disease clearance leads to better results in the long term, there is increasing interest in this outcome.

A post-hoc analysis of the mirikizumab LUCENT-UC studies (the pivotal phase 3, randomized, double-blind, placebo-controlled trials of mirikizumab)  reported the number of patients in CS-free remission, depending on whether they achieved DC at week 12. It showed that 59.1% of the patients who achieved DC under mirikizumab at 12 weeks were in CS-free remission after 1 year, while 40.1% of patients who did not achieve mirikizumab DC at 12 weeks were in CS-free remission after 1 year³. In a Spanish prospective longitudinal cohort (n = 101), which included UC patients with and without anti-TNF treatment, it was also found that patients who achieved DC had a lower risk of negative outcomes (defined as need for therapy or escalation of treatment, hospitalization or colectomy) (Fig 3)⁵. An Argentinian etrospective cohort study (n = 197) found that the combination of a Mayo Endoscopic Subscore of 0-1 and a Nancy Index of 0-1 was associated with better outcomes than achieving only one of these parameters^6.
 

VDZ treatment and treatment effect persistence: main takeaways 

• Several studies report a VDZ treatment persistence of more than 70% after 1 year^9-12
• After 2 years, treatment persistence was 64.2% in a meta-analysis⁹, and 73.3% in the RUN-UC study¹² 
   

UEGW and ECCO provided us with numerous abstracts describing long term outcomes. A meta-analysis of real-world data (publication date 2014-2022) examined treatment persistence under VDZ⁹. This was found to be 72.4% (95% CI 68.7-75.8) after 1 year,and 64.2% (95% CI 55.3-72.2) after 2 years of VDZ. In the included studies, it was found that treatment persistence after 1 year did not differ between bio-naïve and bio-experienced patients: 74.5% (95% CI 66.8-80.9) and 73.1% (95% CI 62.4-81.6) respectively. In this meta-analysis, 42.7% (95% CI 38.4-47.1) of treated patients achieved CS-free clinical remission after 1 year, and in the 29 studies where mucosal healing was reported, 42.6% (95% CI 37.0-48.3) were found to have achieved this endpoint. No safety data was reported in this study, but a second meta-analysis of studies that reported efficacy and treatment patterns of VDZ and anti-TNF in bio-naïve patients did report safety data. In the included studies, serious adverse events (SAE) were reported for VDZ in 4.5%, 6.8% and 14.3% of VDZ-treated patients, while in the same studies, 5%, 19.2% and 10.9% of anti-TNF-treated patients reported SAEs, respectively.¹⁰

At ECCO, a Canadian study reported on the efficacy and persistence of second-line treatment with VDZ (n = 122) and UST (n = 28) after anti-TNF¹¹. In this cohort, 82.3%  of VDZ-treated patients were in clinical remission at 12 months, with 91.5% treatment persistence . In terms of safety, infections were reportedin 4.1% of the patients in the VDZ group, with no serious adverse events reported for either VDZ or UST. The German  prospective, controlled, propensity score-adjusted RUN-UC study included patients treated with UST (n = 153), anti-TNF (n = 165) and VDZ (n = 165). This study reported a VDZ persistence of 73.3% and clinical remission  of 48%  (and 43.9% in bio-experienced patients) after two years of follow-up¹².

For a complete overview of all abstracts presented, please refer to the abstract books: UEG 2024 and ECCO 2025.