Long-term LUCENT-3 data show mirikizumab sustained disease clearance in ulcerative colitis through 4 years of treatment.
New long-term data from the LUCENT-3 open-label extension study suggest mirikizumab (Omvoh) can sustain disease clearance in patients with moderately to severely active
The analysis, presented at
"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 4 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, in a statement.
Disease clearance, as defined in this analysis, represents a composite endpoint requiring the simultaneous achievement of symptomatic remission, endoscopic remission, and histologic remission. Investigators defined symptomatic remission as a Mayo stool frequency subscore of 0 (or 1 with a ≥ 1-point decrease from baseline) and a rectal bleeding subscore of 0. Histologic-endoscopic mucosal remission required a Geboes score of ≤ 2B.0 and an endoscopic subscore of 0 or 1, excluding friability. The composite endpoint sets a higher clinical bar than individual outcome measures assessed in isolation.
Real-world studies have associated disease clearance with reduced rates of UC-related hospitalizations and surgery. 2,3 Notably, Lilly reported that during the 3-year extension period of LUCENT-3, only 1 UC-related hospitalization and 0 UC-related surgeries occurred among patients treated with mirikizumab.1
Investigators evaluated an even more stringent measure, requiring endoscopic normalization, defined as an endoscopic subscore of 0, rather than endoscopic remission. Among patients who met this threshold at 1 year, 61.3% maintained it through 4 years on an observed-cases basis. When a modified nonresponder imputation analysis was applied to account for discontinuation and missing data, the rates were expectedly reduced: 49.7% for disease clearance and 42.8% for stringent disease clearance.1
The LUCENT clinical program evaluated mirikizumab in adults with moderately to severely active UC, including both biologic-naive patients and those with prior failure of a biologic or Janus kinase inhibitor.1
LUCENT-1 served as the randomized, double-blind, placebo-controlled induction study, while LUCENT-2 assessed continued treatment versus placebo among induction responders. LUCENT-3 was a single-arm, open-label extension that followed patients for an additional 3 years beyond LUCENT-2, yielding up to 4 years of total treatment exposure. The disease clearance analysis was conducted post hoc and was not prespecified, a limitation warranting consideration when interpreting durability estimates.1
Regarding safety, the long-term profile in LUCENT-3 was reported as consistent with known safety data for mirikizumab, with no new safety signals. Among patients who completed 1 year of blinded maintenance therapy in LUCENT-2 and entered LUCENT-3, 12% experienced a serious adverse event, and 7% discontinued treatment due to an adverse event. The most common adverse reactions reported at rates of ≥ 2% compared with placebo across the LUCENT program included upper respiratory tract infections, injection site reactions, arthralgia, rash, headache, and herpes viral infections.1
Mirikizumab is a monoclonal antibody that selectively targets the p19 subunit of interleukin-23, inhibiting the IL-23 signaling pathway implicated in the pathogenesis of inflammatory bowel disease.
The therapeutic has received regulatory approvals in 47 countries for moderately to severely active UC and adults with Crohn's disease. In the United States, mirikizumab is also approved for a single-injection maintenance regimen in UC. Eli Lilly and Company has disclosed ongoing combination studies investigating mirikizumab with eltrekibart and zotemtegrast, as well as pediatric trials in both UC and Crohn's disease.1
The post hoc nature of the disease clearance analysis, the open-label study design, and the absence of a comparator arm in LUCENT-3 are important limitations. Whether these findings will influence treatment positioning or guideline recommendations remains to be determined through additional prospective evidence.
