Abstract

Three-Year Efficacy and Safety of Mirikizumab Following 152 Weeks of Continuous Treatment for Ulcerative Colitis: Results From the LUCENT-3 Open-Label Extension Study

Inflamm Bowel Dis. 2024 Oct 25:izae253. doi: 10.1093/ibd/izae253. Online ahead of print.

Bruce E Sands 1Geert D'Haens 2David B Clemow 3Peter M Irving 4Jordan T Johns 3Theresa Hunter Gibble 3Maria T Abreu 5Scott D Lee 6Tadakazu Hisamatsu 7Taku Kobayashi 8Marla C Dubinsky 9Severine Vermeire 10Corey A Siegel 11Laurent Peyrin-Biroulet 12 13 14Richard E Moses 3Joe Milata 3Remo Panaccione 15Axel Dignass 16

 
     

Author information

1Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

2Amsterdam University Medical Centers, Amsterdam, The Netherlands.

3Eli Lilly and Company, Indianapolis, IN, USA.

4Guy's and St. Thomas' NHS Foundation Trust, London, King's College, London, UK.

5UHealth Crohn's and Colitis Center, University of Miami Miller School of Medicine, Miami, FL, USA.

6Digestive Health Center, University of Washington Medical Center, Seattle, WA, USA.

7Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan.

8Center for Advanced IBD Research and Treatment, Kitasato University, Kitasato Institute Hospital, Tokyo, Japan.

9Icahn School of Medicine at Mount Sinai, New York, NY, USA.

10Department of Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium.

11Dartmouth Hitchcock Medical Center, Lebanon, NH, USA.

12Department of Gastroenterology, INFINY Institute, FHU-CURE, INSERM NGERE, Nancy University Hospital, Nancy, France.

13Groupe Hospitalier Privé Ambroise Paré-Hartmann, Paris IBD Center, Neuilly-sur-Seine, France.

14Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada.

15Inflammatory Bowel Disease Group, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

16Department of Medicine I, Agaplesion Markus Krankenhaus, Frankfurt, Germany.

Abstract

Background: Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, has demonstrated induction of clinical remission at week 12 with maintenance through week 104 in patients with moderately-to-severely active ulcerative colitis (UC). Results are presented from the LUCENT-3 open-label extension study through week 152.

Methods: Of 868 LUCENT clinical trial program mirikizumab-treated induction patients, 544 were responders of whom 365 were rerandomized to mirikizumab maintenance. Of these, 324 completed week 52 and 316 entered extension treatment (286 week 52 responders; 179 week 52 remitters). Efficacy and safety outcomes are reported for mirikizumab-treated LUCENT-3 participants, including biologic-failed patients, with data for week 52 maintenance responders/remitters. Discontinuations or missing data were handled by nonresponder imputation, modified nonresponder imputation (mNRI), and observed cases.

Results: Using mNRI, 81.6% of week 52 responders demonstrated clinical response at week 152. Week 152 remission rates for week 52 responders included clinical (56.1%), corticosteroid-free (CSF; 54.5%), endoscopic (61.0%), histologic-endoscopic mucosal remission (HEMR; 52.6%), symptomatic (74.9%), and bowel urgency (BU; 58.6%). At week 152, 53.3% of week 52 responders achieved histologic-endoscopic mucosal improvement (HEMI) and 74.3% achieved BU clinically meaningful improvement (CMI). Among week 52 remitters, 85.4% showed a clinical response at week 152, with clinical (70.1%), CSF (68.9%), endoscopic (72.0%), HEMR (63.4%), symptomatic (81.4%), and BU (60.8%) remission. At week 152, among week 52 remitters, 64.0% of patients achieved HEMI and 75.6% achieved BU CMI. Stool frequency, rectal bleeding, BU, and abdominal pain score reductions from induction baseline to maintenance week 52 were sustained through week 152 for week 52 completers. Overall, in the safety population, 7.4% of patients reported severe adverse events (AEs); 5.3% discontinued treatment due to AEs. AEs of special interest included opportunistic infection (1.8%), hepatic disorders (3.2%), cerebrocardiovascular events (1.5%), and malignancy (0.3%). Patients with antidrug antibodies reduced over time from 23.6% in year 1 to 3.2% in year 3.

Conclusions: Symptomatic, clinical, endoscopic, histologic, and quality-of-life outcomes support long-term sustained benefit of mirikizumab treatment up to 152 weeks in patients with UC, including biologic-failed patients, with no new safety concerns.

Clinical trial registry: ClinicalTrials.gov: NCT03518086NCT03524092NCT03519945.

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