Jean-Frederic Colombel, MD, on Disease Clearance With Mirikizumab in Ulcerative Colitis

Dr Colombel discusses his presentation at DDW 2026 on a post-doc analysis of the long-term outcomes of the LUCENT trial of mirikizumab, which showed that the IL-23p19 inhibitor achieved and maintained disease clearance for up to 4 years among patients with ulcerative colitis.

Jean-Frederic Colombel, MD, is the director of the Inflammatory Bowel Disease Center at Icahn School of Medicine at Mount Sinai in New York.

Mirikizumab (IL-23 antagonist) in Moderately to Severely Active Ulcerative Colitis: 4-Year Disease Clearance Outcomes from LUCENT Post Hoc Analysis (DDW, US)

• Ulcerative colitis; mirikizumab (IL-23 antagonist); LUCENT trial (randomized, placebo-controlled); post hoc long-term analysis: Among a selected cohort of patients treated with  mirikizumab from baseline, who achieved clinical response at week 12, remission at 1 year, then continued maintenance, the majority maintained disease clearance—defined as combined symptomatic, endoscopic, and histologic remission—through 4 years of follow-up, supporting sustained maintenance efficacy after early remission.
• Endpoints and durability (4-year timeframe): Using stringent definitions, approximately 30–40% of patients achieved this strict disease clearance at 4 years, although some loss of response occurred; overall durability on therapy remained notable in this responder-enriched population.
• Safety and clinical implications: No new safety signals were identified over 4 years, indicating a favorable long-term safety profile; findings suggest that achieving remission by 1 year may predict sustained long-term control, while the VERDICT trial (ongoing) will clarify optimal treatment targets (clinical vs endoscopic vs histologic remission) and impact on long-term outcomes (e.g., colectomy, hospitalization).

My name is Jean-Frederic Colombel. I'm the director of the Inflammatory Bowel Disease Center at Icahn School of Medicine at Mount Sinai in New York. So the study that I presented at DDW this year is entitled Mirikizumab Demonstrates Consistent and Sustained Disease Clearance at Four Years of Treatment in Patients With Moderately to Severely Active Ulcerative Colitis. This is a post-doc analysis looking at the long-term outcomes of the LUCENT trial. The LUCENT trial was a study performed in patients with moderately to severely active ulcerative colitis who were randomized to receive mirikizumab, which is an IL-23 antagonist and placebo. So the study, the original study, demonstrated efficacy of mirikizumab for induction and for maintenance of response and remission in ulcerative colitis.

What I have been presented today is a long-term outcome. And for this long-term outcome, there are two very important points to mention.

First, we only look at the participants in the study who receive only mirikizumab from the beginning. Then they were in clinical response at week 12. Then they were randomized to receive mirikizumab as maintenance. And then they were in remission at one year and they were subsequently followed up. So in other words, it's a kind of selection of patients who did well on the drug. And the goal was to look at the long-term outcomes. The question is, how long did they do well?

And in order to look at very stringent endpoint, we looked at this very interesting concept, which is called disease clearance. As you know, in ulcerative colitis, there are different endpoints, clinical endpoints, which is symptomatic remission; endoscopic endpoint, which is endoscopic remission; and histological endpoint. And basically, the disease clearance is a kind of combination of everything, meaning that you are able to achieve symptomatic endoscopic and histological remission.

So what we basically showed in this post-doc study is that in patients who were able to achieve remission at one year, so we're in remission at one year, most of those patients, the majority of those patients were able to maintain disease clearance further on until year 4. Of course, some patients lost response, but overall there was a remarkable maintenance on drug, which is a testimony of the good efficacy of this drug for maintenance when the remission has been achieved at one year.

So why is it important? It's important because of course, as you know, when we are treating patients with ulcerative colitis, we are always considering long-term. As we always say, it's not a sprint, but it's a marathon. And it's showing that if you are able to achieve remission early, actually the chance of remaining in remission and even in disease clearance at 4 years is relatively important.

Very important point as well, there was no new safety signal, meaning that it's also key to mention that this is a safe drug, able to maintain in the long-term and with a good safety profile.

Coming back to this outcome of disease clearance, I think it's fair to say that we don't know if this is the next target to achieve in ulcerative colitis because it's very stringent, and we still don't know what's best target to achieve in ulcerative colitis. And as a matter of fact, we will get this year later on the result of the VERDICT trial, which should be able to answer this question because in that study, we prospectively randomize patient with ulcerative colitis and treat them in order to achieve clinical remission or endoscopic remission or endoscopic and histological remission. And we looked at their long-term outcomes. So bottom line, to see if we are able to change the natural history of the disease—less colectomy, hospitalization, surgeries. And this study is very important because it will tell us, yes, you need to treat to endoscopic killing or treat to clinical remission is good enough.

So in advance of this study, the data that are presented during this meeting is showing that mirikizumab could be one of the drugs used to maintain long-term clearance and long-term remission in patient with UC and maybe change their natural history, even though this was not fully addressed in this study. To go a little bit more in the detail, we use two definition of disease clearance: a classical one, which was symptomatic remission, endoscopic remission, with a Mayo score of one of 01, and what we call mucosal healing, which is histo and low remission. But we even use a more stringent endpoint, a kind of modified definition of disease clearance, more stringent, where we only consider patients who are able to achieve an endoscopic score of zero. And even though the percentages of patients were less at the end of four years, still there was a very good number of patients, approximately 30 to 40% were able to achieve this very strict definition of disease clearance at 4 years.