P4355 - Long-Term Efficacy and Safety of Mirikizumab Following 152 Weeks of Continuous Treatment: Results From the LUCENT-3 Open-Label Extension Study

Bruce E.. Sands, MD, FACG¹, Geert R. D'Haens, MD, PhD², David Clemow, ³, Peter Irvin, ⁴, Jordan Johns, ³, Theresa Gibble, PhD³, Maria Abreu, ⁵, Scott Lee, ⁶, Tadakazu Hisamatsu, MD, PhD⁷, Taku Kobayashi, MD⁸, Marla C. Dubinsky, MD¹, Séverine Vermeire, MD, PhD⁹, Corey A.. Siegel, MD, MS¹⁰, Laurent Peyrin-Biroulet, MD, PhD¹¹, Richard Moses, ³, Joe Milata, ³, Vipin Arora, ³, Axel Dignass, MD, PhD¹², Remo Panaccione, MD^13
1Icahn School of Medicine at Mount Sinai, New York, NY; ²Amsterdam University Medical Center, Amsterdam, Limburg, Netherlands; ³Eli Lilly and Company, Indianapolis, IN; ⁴Guy's and St. Thomas’ Hospitals, London, King's College, London, England, United Kingdom; ⁵UHealth Crohn’s and Colitis Center, University of Miami Miller School of Medicine, Miami, NE; ⁶Digestive Health Center University of Washington Medical Center, Seattle, WA; ⁷Kyorin University School of Medicine, Tokyo, Tokyo, Japan; ⁸Kitasato University Kitasato Institute Hospital, Minato City, Tokyo, Japan; ⁹University Hospitals Leuven, Leuven, Vlaams-Brabant, Belgium; ¹⁰Dartmouth-Hitchcock Medical Center, Lebanon, NH; ¹¹INFINY Institute, FHU-CURE, INSERM NGERE, Nancy University Hospital, Vandœuvre-lès-Nancy, Lorraine, France; McGill University Health Centre, Montreal, QC, Canada, Nancy, Lorraine, France; ¹²Agaplesion Markus Hospital, Goethe University, Frankfurt, Hessen, Germany; ¹³University of Calgary, Calgary, AB, Canada

Introduction: Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, is efficacious in inducing clinical remission at Week(W) 12 and maintaining clinical remission through W52 and W104 in patients with moderately-to-severely active ulcerative colitis (UC) (LUCENT-1, LUCENT-2, LUCENT-3). Here we present efficacy and safety results through W152 of mirikizumab treatment from the open-label extension LUCENT-3 study.

Methods: Clinical, symptomatic, quality-of-life, and adverse event outcomes are reported for mirikizumab induction responders, including biologic failed patients, who entered LUCENT-3, with data shown for W52 maintenance responders or remitters. Discontinuations or missing data were handled by non-responder imputation (NRI), modified NRI (mNRI), and observed case (OC). mNRI uses multiple imputation for missing data and balances bias of NRI and OC. Table provides endpoint and population definitions and abbreviations.

Results: Using mNRI, among W52 miri responders, 82% demonstrated clinical response at W152. Remission rates at W152 for W52 clinical responders were: 56% clinical, 55% corticosteroid-free (CSF), 61% endoscopic, 53% histologic-endoscopic mucosal remission (HEMR), 75% symptomatic, and 59% bowel urgency. Patients achieving histologic-endoscopic mucosal improvement (HEMI) and bowel urgency clinically meaningful improvement (CMI) at W152 were 53% and 74%, respectively. For W52 miri remitters, 85% demonstrated clinical response at W152. Remission rates at W152 for W52 clinical remitters were: 70% clinical, 69% CSF, 72% endoscopic, 63% HEMR, 82% symptomatic, and 61% bowel urgency. Patients achieving HEMI and bowel urgency CMI at W152 were 64% and 76%, respectively. Biologic Failed/Non-failed subgroup data were generally similar (Table). Stool frequency, rectal bleeding, bowel urgency, and abdominal pain symptom score reductions from induction baseline at W52 were sustained through W152. Severe adverse events (AEs) were reported in 7.4% of patients, while 5.3% discontinued treatment due to an AE. AEs of special interest included: opportunistic infection (1.8%); cerebrocardiovascular events (1.5%); malignancy (0.3%). Elevated liver enzymes ≥3ULN included: ALT (0.9%); AST (1.2%); TBL (1.8%); none ≥5ULN.

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


Disclosures:


Bruce E.. Sands, MD, FACG¹, Geert R. D'Haens, MD, PhD², David Clemow, ³, Peter Irvin, ⁴, Jordan Johns, ³, Theresa Gibble, PhD³, Maria Abreu, ⁵, Scott Lee, ⁶, Tadakazu Hisamatsu, MD, PhD⁷, Taku Kobayashi, MD⁸, Marla C. Dubinsky, MD¹, Séverine Vermeire, MD, PhD⁹, Corey A.. Siegel, MD, MS¹⁰, Laurent Peyrin-Biroulet, MD, PhD¹¹, Richard Moses, ³, Joe Milata, ³, Vipin Arora, ³, Axel Dignass, MD, PhD¹², Remo Panaccione, MD¹³. P4355 - Long-Term Efficacy and Safety of Mirikizumab Following 152 Weeks of Continuous Treatment: Results From the LUCENT-3 Open-Label Extension Study, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.