Mirikizumab Shows Sustained Benefit in Ulcerative Colitis Treatment Advances

Mirikizumab demonstrated long-term sustained benefit in symptomatic, clinical, endoscopic, histologic, and quality-of-life outcomes among patients with ulcerative colitis (UC) for up to 152 weeks with no new safety concerns, according to findings from the open-label extension LUCENT-3 study.

The authors of the poster presented at the United European Gastroenterology conference in October 2024 added that these benefits were seen in patients who had not responded to, lost response to, or were intolerant of biologic therapies.

Mirikizumab is a p19-directed interleukin-23 monoclonal antibody that proved efficacious in inducing clinical remission at Week 12 and maintaining clinical remission through Weeks 52 and 104 in patients with moderately-to-severely active UC during the LUCENT-1 and LUCENT-2 trials.

Discontinuations or missing data were handled by nonresponder imputation (NRI), modified NRI (mNRI), and observed case (OC). mNRI uses multiple imputation for missing data and balances bias of NRI and OC.

Among week 52 responders to mirikizumab, 82% demonstrated clinical response at week 152. Remission rates at week 152 for week 52 clinical responders were 56% clinical, 55% corticosteroid-free (CSF), 61% endoscopic, 53% histologic-endoscopic mucosal remission (HEMR), 75% symptomatic, and 59% bowel urgency.

At week 152, 53% of patients achieved histologic-endoscopic mucosal improvement (HEMI) and 74% achieved clinically meaningful improvement (CMI) in bowel urgency. For week 52 mirikizumab remitters, 85% demonstrated clinical response at week 152, with remission rates of 70% clinical, 69% CSF, 72% endoscopic, 63% HEMR, 81% symptomatic, and 61% bowel urgency. Patients achieving HEMI and bowel urgency CMI at week 152 were 64% and 76%, respectively.

Maintenance of efficacy with mirikizumab was demonstrated in subgroup data for patients who had failed biologic therapy and those who had not. Stool frequency, rectal bleeding, bowel urgency, and abdominal pain symptom score reductions from induction baseline at week 52 were sustained through week 152. Severe adverse events (AEs) were reported in 7.4% of patients; 5.3% discontinued treatment due to an AE. Opportunistic infection (1.8%), cerebrocardiovascular events (1.5%), and malignancy (0.3%) were noted as AEs of special interest. Elevated liver enzymes at or above 3 upper limit of normal (ULN)

included alanine aminotransferase (0.9%), aspartate aminotransferase (1.2%); 2xULN total bilirubin (1.8%), alkaline phosphatase (0.6%), gamma-glutamyltransferase (2.9%); ≥5 ULN: AST (0.3%).

Reference:

Sands BE, D’Haens GR, Clemow D, et al. MP617: Long-term efficacy and safety of mirikizumab following 152 weeks of continuous treatment: results from the LUCENT-3 open-label extension study. Presented at: United European Gastroenterology Week. October 13, 2024. Published in United European Gastroenterol J. 2024;12 (S8): 585-586.