Vipul Jairath, MBChB, DPhil: The ‘Evolving Concept’ of Disease Clearance in Ulcerative Colitis

Defined as concurrent achievement of clinical, endoscopic, and histologic remission, the concept of disease clearance in ulcerative colitis (UC) sets a high bar for treatments and thus far remains elusive.

The VERDICT trial seeks to address unanswered questions about optimal treatment targeting in this patient population, subsequently informing clinical practice, drug trials, and future evidence-based recommendations. Interim results were presented at the European Crohn’s and Colitis Organisation (ECCO) Congress annual meeting in Stockholm, Sweden.¹

“We don't have a cure for the condition other than surgery to move the large bowel, so the treatments are there to try and improve symptoms. The concept of disease clearance is a terminology that's recently evolved,” Vipul Jairath, MBChB, DPhil, John and Susan McDonald Endowed Chair in Inflammatory Bowel Disease Clinical Research at Western University and Chief Medical Officer at Alimentiv, said in an interview with HCPLive, explaining its similarity to endpoints used in other inflammatory diseases like rheumatoid arthritis.

“What it essentially means is at the time that you assess a patient, you don't see any inflammation. Number one, their symptoms have disappeared, and that's normal. Number two, when you do the endoscopy, which is typically a colonoscopy, you don't see inflammation. And number three, when you take biopsies and look under the microscope, you see absolutely no inflammation whatsoever.”

However, Jairath noted it is uncertain whether this necessarily translates to better outcomes for patients, a question the VERDICT trial seeks to answer by determining optimal treatment targets and whether existing drugs have the ability to reach those targets.

A multicenter, randomized, controlled trial, VERDICT aims to determine the optimal treatment target in UC by comparing a trio of target groups: Group 1 (corticosteroid-free symptomatic remission), Group 2 (corticosteroid-free symptomatic remission + endoscopic improvement), and Group 3 (corticosteroid-free symptomatic remission + endoscopic improvement + histologic remission). Study participants were randomly assigned to each of these treatment targets in a 5:4:1 ratio, with therapy administered according to a treatment algorithm dependent on each patient’s existing UC treatment regimen at study entry.¹

Across all 3 algorithms, early introduction of vedolizumab and dose escalation to a maximum of 300 mg every 4 weeks until the assigned treatment target is reached is central to the treatment regimen. There are 3 opportunities at weeks 16, 32, and 48 to achieve the treatment target. At baseline and during these follow-up time points, urine, stool, mucosa, and serum samples are collected for subsequent biomarker and prediction model development.¹

The achievement of corticosteroid-free disease clearance at week 16 in Group 3 was reported at ECCO, defined as a Mayo rectal bleeding subscore of 0, endoscopic improvement (Mayo Endoscopic Score ≤ 1), and histologic remission (Geboes score < 2B.0).¹

As of August 18, 2023, 553 patients were enrolled in VERDICT with 253 assigned to target Group 3. The group had a mean age of 41.2 (standard deviation [SD] 14.3) years, mean disease duration of 7.3 (SD, 7.8) years, and 42% were female. In total, 216 (85%) were bionaïve, 159 (63%) had a baseline Mayo Endoscopic Score of 3, and 129 (51%) were receiving concomitant corticosteroids.¹

At the time of analysis, remission target status was unavailable for 30 bionaïve and 11 bio-exposed patients. Among the 212 patients with observed data, 86 (41%) achieved corticosteroid-free remission, including 77 (41%) of the 186 bionaïve patients with data and 9 (35%) of the 26 bio-exposed patients with data.¹

Corresponding values of achieving corticosteroid-free disease clearance in the intention-to-treat population were 34% (86/253), 36% (77/216), and 24% (9/37), respectively. All patients with disease clearance were receiving vedolizumab treatment from baseline.¹

“They're novel data, and they're higher than any rates that we've seen with other drugs, notwithstanding that not many other drugs have measured this at this point because it's quite an evolving concept,” Jairath said, although he was careful to point out the results presented at ECCO were preliminary and patient outcomes have not been measured thus far: “It will be a couple of years before we have the answers, but it's important for the field to understand this because it will inform the way we treat patients and potentially the way we develop new drugs.”

Reference:

1. ^{Jairath V, Zou G, Adsul S, et al. DOP11 Disease clearance after 16 weeks of treatment with vedolizumab in patients with moderate to severe Ulcerative Colitis: An interim analysis from the VERDICT trial. Journal of Crohn's and Colitis. https://doi.org/10.1093/ecco-jcc/jjad212.0051}