Mirikizumab Sustains UC Disease Clearance at Four Years in LUCENT-3 Extension Data

More than 60% of patients with moderately to severely active ulcerative colitis (UC) who achieved disease clearance at one year on mirikizumab-mrkz (Omvoh; Eli Lilly) sustained that composite endpoint through four years of continuous treatment, according to new long-term data from the LUCENT-3 open-label extension study presented at Digestive Disease Week 2026. The findings represent the first demonstration of durable disease clearance at four years for any interleukin-23p19 (IL-23p19) inhibitor in UC—a distinction that may carry meaningful implications for how clinicians frame long-term treatment goals in this population.¹

"What makes these data so compelling is that they go beyond individual measures of improvement to show that patients treated with Omvoh achieved disease clearance, with simultaneous symptomatic, endoscopic and histologic remission, maintained over four years," said Jean-Frédéric Colombel, MD, director of the Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center at the Icahn School of Medicine at Mount Sinai. "For a progressive disease like ulcerative colitis, that level of durable remission has the potential to change the long-term course of the disease for patients."

Trial and Regulatory Overview

Mirikizumab was evaluated in the three-part LUCENT clinical trial program. LUCENT-1 was a randomized, double-blind, placebo-controlled induction study enrolling adults with moderately to severely active UC who had an inadequate response, loss of response, or intolerance to corticosteroids, immunomodulators, biologic therapy, or Janus kinase inhibitors (JAKi). LUCENT-2 assessed continued maintenance therapy versus placebo in clinical responders from LUCENT-1. LUCENT-3 is a single-arm, open-label Phase 3 extension study that enrolled patients completing LUCENT-1 and LUCENT-2 and followed them for an additional three years—four years of cumulative treatment in total.⁵

The new analysis presented at DDW 2026 evaluated disease clearance as a composite endpoint, defined as simultaneous symptomatic remission (Mayo stool frequency score of 0 or 1 with ≥1-point decrease from baseline, and rectal bleeding score of 0), endoscopic remission (endoscopic subscore of 0 or 1, excluding friability), and histologic remission (Geboes score ≤2B.0). Among patients who achieved this composite at one year, 63.5% maintained it at four years using observed cases in a post hoc analysis. A more stringent definition requiring endoscopic normalization (endoscopic subscore of 0) was sustained at four years by 61.3% of those who had achieved it at one year.¹ Using a modified non-responder imputation method to account for discontinuations and missing data, rates were 49.7% and 42.8% for standard and stringent disease clearance, respectively.¹

Importantly, this composite endpoint analysis was not pre-specified, a methodological limitation that warrants interpretive caution.

The long-term safety profile was consistent with previously established data. Among patients who completed LUCENT-2 and entered LUCENT-3, 12% reported a serious adverse event and 7% discontinued treatment due to an adverse event. The most commonly reported adverse reactions (occurring in ≥2% of patients at higher frequency than placebo across LUCENT-1 and LUCENT-2) included upper respiratory tract infections, injection site reactions, arthralgia, rash, headache, and herpes viral infection.⁶ No new safety signals were identified. One UC-related hospitalization and zero UC-related surgeries were reported during LUCENT-3.⁴

Clinical Context

UC is a chronic, relapsing inflammatory bowel disease characterized by diffuse mucosal inflammation of the colon. Management goals have evolved substantially over the past decade, moving beyond symptom control toward deeper endpoints including endoscopic and, more recently, histologic remission. Real-world data suggest that achieving disease clearance—as a composite of these measures—is associated with reduced rates of hospitalizations and surgery.²,³ Sustaining this level of disease control over multiple years represents a meaningful, if aspirational, treatment target.

Drug and Drug-Class Background

Mirikizumab selectively targets the p19 subunit of IL-23, inhibiting a cytokine pathway central to the pathogenesis of inflammatory bowel disease. The agent received regulatory approval in the United States and has been approved in 47 countries for moderately to severely active UC and Crohn's disease in adults. In the US, mirikizumab is also approved for a single-injection maintenance regimen in UC.⁶

Limitations and Next Steps

The LUCENT-3 disease clearance analysis is post hoc and not pre-specified, which limits the strength of inference that can be drawn. Open-label extension studies lack placebo controls, making it difficult to isolate treatment effects from natural disease variation or regression to the mean. Lilly is pursuing combination strategies pairing mirikizumab with eltrekibart (NCT06598943), zotemtegrast (NCT07186101), and incretin-based therapies (COMMIT-UC, NCT06937086; COMMIT-CD, NCT06937099), as well as pediatric trials in both UC and Crohn's disease.

References

1. Magro F, et al. Mirikizumab demonstrates consistent and sustained disease clearance at four years of treatment in patients with moderately to severely active ulcerative colitis. Digestive Disease Week 2026. May 2–5, 2026.
2. Andronic AM, et al. J Crohns Colitis. 2023;17(suppl 1):i529. https://doi.org/10.1093/ecco-jcc/jjac190.0528
3. Pai RK, et al. Expert Rev Gastroenterol Hepatol. 2024;18(1-3):73–87. https://doi.org/10.1080/17474124.2024.2326838
4. Magro F, et al. J Crohns Colitis. 2026;20(suppl 1):jjaf231.1300. https://doi.org/10.1093/ecco-jcc/jjaf231.1300