Jean-Frederic Colombel, MD, is the Director of the Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center at the Icahn School of Medicine at Mount Sinai.

Jean-Frederic Colombel, MD

Mirikizumab Demonstrates Sustained Disease Clearance Through 4 Years in Ulcerative Colitis

Long-term results from the LUCENT clinical trial program suggest that mirikizumab maintains consistent and sustained disease clearance over 4 years in patients with moderately to severely active

2026 by Jean Frédéric Colombel, MD, Professor Of Medicine and the Director of the Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center at the Icahn School of Medicine at Mount Sinai.

Mirikizumab, an interleukin-23 (IL-23) p19 inhibitor, has demonstrated efficacy across both induction and maintenance phases in ulcerative colitis, aligning with its role in a growing class of advanced biologics targeting key inflammatory pathways.

“As a matter of fact, there are now a lot of data that have established efficacy for induction and maintenance of response and remission with mirikizumab,” Colombel said in an interview with 

, situating the agent within the current treatment landscape.

Disease Clearance as a Multidimensional Treatment Target

The analysis focused on patients who achieved clinical remission at week 52 and entered the open-label extension study, LUCENT-3 (NCT03519945), with outcomes assessed through 4 years of maintenance therapy.

Colombel emphasized the evolving framework for defining treatment success in UC, describing a layered model of disease activity.

“You know, at the top you have what we call a clinical remission. And then if you go deeper, you have endoscopic, and then if you go even deeper, you have histological remission,” he explained. “When you combine all these different endpoints, you arrive to this concept… disease clearance includes symptomatic, endoscopic, and histologic remission. So it's basically the most stringent endpoint that you can think about in ulcerative colitis.”

Disease clearance (DC) was defined as symptomatic remission combined with histologic-endoscopic mucosal remission (HEMR), including histologic remission (Geboes score ≤2B.0) and endoscopic remission (Mayo endoscopy subscore of 0 or 1, excluding friability).

A more stringent endpoint (sDC) required symptomatic remission, histologic remission, and endoscopic normalization (score of 0).

Among week 52 maintenance remitters, disease clearance remained durable through 4 years of continuous mirikizumab therapy.

75.6% / 75.4% (mNRI / observed cases) at year 1

For stringent disease clearance (sDC), rates were:

Despite expected attrition over time, more than 60% of patients maintained DC at year 4 using observed cases, and over 40% achieved sDC.

Colombel noted that these results are consistent with what is seen in good responders to IL-23–targeted therapy.

“Very simple message is that there was very good maintenance of this disease clearance endpoint at four years, which I think is quite remarkable, which is a testimony of the efficacy of this drug for maintaining patients in long-term remission,” he said.

He added that early response appears to be a key marker of long-term durability, though predictive factors remain unclear.

“If you are able to achieve remission and even further disease clearance relatively early, there is good likelihood that you will be able to maintain it,” Colombel said. “What we still don't know is who are those patients… how can we predict short-term remission and then maintenance of long-term remission?”

Clinical Implications and Disease Modification Potential

The findings also contribute to ongoing discussions around whether modern biologics are altering the natural history of ulcerative colitis.

Colombel pointed to broader population-level trends suggesting reduced rates of colectomy and complications in the biologic era.

“Yes, I’m almost certain that we are changing the natural history of the disease thanks to the new drugs that we have,” he said. “We already have data showing that the rate of colectomy has decreased in population-based studies.”

However, he emphasized that unmet need remains, particularly among patients with multiple lines of treatment failure who still progress to surgery.

Safety Profile Remains Stable Over 4 Years

In addition to efficacy, long-term safety remained consistent across the 4-year observation period, with no new safety signals identified.

Colombel highlighted the importance of sustained tolerability in chronic therapy.

“Even though it’s not mentioned here, the safety of this drug looks very good,” he said. “When we observed those patients for four years, we didn’t see any new safety signal, which I think is very good.”

Across 4 years of follow-up in the LUCENT-3 extension study, mirikizumab demonstrated sustained disease clearance in a substantial proportion of patients with moderately to severely active ulcerative colitis. These results reinforce its role as a durable therapeutic option capable of maintaining deep remission across clinical, endoscopic, and histologic domains, while supporting ongoing efforts to refine treat-to-target strategies in UC.

Editor’s Note: Colombel reports relevant disclosures with AbbVie, Janssen Pharmaceuticals, Takeda, and others.

Magro F, Danese S, Siegmund B, Kobayashi T, Siegel CA, Jairath V, et al. Mirikizumab demonstrates consistent and sustained disease clearance at four years of treatment in patients with moderately to severely active ulcerative colitis. Presented at: 

Sands BE, D’Haens G, Clemow DB, et al. Four-year efficacy and safety of mirikizumab in moderately to severely active ulcerative colitis: results from the LUCENT-3 open-label extension study. 

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Colombel discusses long-term LUCENT extension data showing durable clinical, endoscopic, and histologic outcomes with mirikizumab in moderately to severely active UC.


Jean-Frederic Colombel, MD

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