P1069 - Mirikizumab Improves Bowel Urgency and Correlates With Patient-Reported Outcomes in Moderately-to-Severely Active Ulcerative Colitis: LUCENT-URGE Trial

Silvio Danese, MD, PhD¹, Axel Dignass, MD, PhD², David Laharie, ³, Jimmy Limdi, MD⁴, Radoslaw Kempinski, MD, PhD⁵, James D. Lewis, MD⁶, Erica R. Cohen, MD⁷, Karla Alaka, ⁸, William J. Eastman, ⁸, Tian Tian, ⁸, Isabel Redondo, MD⁸, David T. Rubin, MD⁹, Marla C. Dubinsky, MD¹⁰
1Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Lombardia, Italy; 2Agaplesion Markus Hospital, Frankfurt, Hessen, Germany; 3CHU de Bordeaux, Centre Medico-chirurgical Magellan, Hôpital Haut-Lévêque, Gastroenterology Department; Université de Bordeaux, Pessac, Aquitaine, France; 4Northern Care Alliance NHS Foundation Trust and University of Manchester, Manchester, England, United Kingdom; 5Wrocław Medical University, Wrocław, Lubelskie, Poland; 6Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; 7Capital Digestive Care, Chevy Chase, Maryland, MD, USA, Chevy Chase, MD; 8Eli Lilly and Company, Indianapolis, IN; 9University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, USA, Chicago, IL; 10Susan and Leonard Feinstein IBD Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA, New York, NY

Introduction: Mirikizumab (miri) is an anti-IL-23p19 monoclonal antibody approved for the treatment of ulcerative colitis (UC) and Crohn’s disease. LUCENT-URGE (NCT05767021) is a multicenter, open-label, single-arm miri Phase 3b study in patients with moderately-to-severely active UC. LUCENT-URGE aimed to further explore the impact of miri on bowel urgency (BU). This analysis examined the relationship between the BU assessments and other symptoms associated with UC.

Methods: Patients with UC and baseline BU (UNRS ≥3) were treated with intravenous miri 300 mg at week (W)0, W4, and W8, followed by subcutaneous miri 200 mg at W12, W16, W20, and W24. BU measures included the validated Urgency Numerical Rating Scale (UNRS) and the novel assessments of BU Frequency (BUF) and Shortest Weekly Stool Deferral Time (SDT). Additional patient-reported symptoms and tools used to collect patient-reported outcomes included Stool Frequency (SF), Rectal Bleeding (RB), Nocturnal Stool (NS), Abdominal Pain (AP) NRS, Fatigue NRS, Patient’s Global Rating of Severity (PGR-S), and Patient's Global Impression of Change (PGI-C). The Spearman correlation coefficient (95% confidence interval) was calculated to assess the correlation between continuous BU measures and UC symptoms measures at Baseline, W12, and W28.

Results: BU and UC symptoms measures improved from Baseline to W12 and maintained improvements through W28 (Table 1). The UNRS, BUF, and SDT measures generally showed stronger correlations with other patient-reported measures at W12 and W28 compared to Baseline (Table 2). The strongest correlations were observed between the UNRS and BUF measures and SF, AP NRS, and Fatigue NRS. The BU measures were less associated with RB alone. SF measures demonstrated moderate correlations with UNRS and BUF. Fatigue NRS had a moderate correlation with UNRS throughout. PGR-S had moderate correlations with UNRS and weak correlations with BUF and SDT at Baseline, which increased to moderate by W28. All 3 BU measures showed moderate correlation with the PGR-S by W28.

Discussion: In patients with moderately to severely active UC treated with miri, improvements in all BU measures at W12 were sustained and improved through Week 28. Most correlation levels between BU measures and other symptoms were similar or increased during the study. Moderate correlations between all 3 BU measures and PGRS support that BU is an important component of patients’ overall symptom burden.


Figure: Table 1. BU and UC Symptom Measures at Baseline, Week 12, and Week 28 (BOCF)


Figure: Table 2. Correlations between Bowel Urgency Measures and UC Symptom Measures

Disclosures:
Silvio Danese: AbbVie – Consultant, Lecture fees. Alimentiv – Consultant. Allergan – Consultant. Amgen – Consultant, Lecture fees. AstraZeneca – Consultant. Athos Therapeutics – Consultant. Biogen – Consultant. Boehringer Ingelheim – Consultant. Celgene – Consultant. Celltrion – Consultant. Eli Lilly – Consultant. Enthera – Consultant. F. Hoffmann-La Roche Ltd – Consultant. Ferring Pharmaceuticals Inc. – Consultant, Lecture fees. Gilead – Consultant, Lecture fees. Hospira – Consultant. Inotrem – Consultant. Johnson & Johnson – Consultant, Lecture fees. MSD – Consultant. Mundipharma – Consultant. Mylan – Consultant, Lecture fees. Pfizer – Consultant, Lecture fees. Sandoz – Consultant. Sublimity Therapeutics – Consultant. Takeda – Consultant, Lecture fees. TiGenix – Consultant. UCB Inc. – Consultant. Vifor (International) Ltd. – Consultant.
Axel Dignass: Abbvie – Consultant, fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis and endpoint committees; manuscripts, Speakers Bureau. Abivax – fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis and end point committees. Amgen – Consultant. Arena Pharmaceuticals – Consultant. Biogen – Consultant, Speakers Bureau. Boehringer Ingelheim – Consultant. Bristol Myers Squibb – Consultant. CED Service GmbH – Speakers Bureau. Celltrion – Consultant, Speakers Bureau. Dr Falk Foundation – Consultant, fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis and endpoint committees; manuscripts, Speakers Bureau. Ferring – Consultant, Speakers Bureau. Fresenius Kabi – Consultant. Galapagos – Consultant, fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis and end point committees, Speakers Bureau. Gilead – fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis and end point committees, Speakers Bureau. High5MD – Speakers Bureau. Johnson & Johnson – Consultant, fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis and endpoint committees; manuscripts, Speakers Bureau. Lilly – Consultant. Materia – Speakers Bureau. MedToday – Speakers Bureau. MSD – Consultant, Speakers Bureau. Pfizer – Consultant, fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis and end point committees, Speakers Bureau. Pharmacosmos – Consultant. Prima – Speakers Bureau. Roche – Consultant. Sandoz – Consultant. Stada – Consultant. Takeda – Consultant, manuscript preparation, Speakers Bureau. Thieme – manuscript preparation. Tilliots – Consultant, Speakers Bureau. UniMed Verlag – manuscript preparation. Vifor Pharma – Consultant, Speakers Bureau.
David Laharie: AbbVie – Advisory Committee/Board Member, Consultant, Transport, Fees.. Alfasigma – Advisory Committee/Board Member, Consultant, Transport or Fees. Amgen – Advisory Committee/Board Member, Consultant, Transport, Fees.. Celltrion – Advisory Committee/Board Member, Consultant, Transport, Fees.. Eli Lilly and Company – Advisory Committee/Board Member, Consultant, Transport, Fees.. Ferring Pharmaceuticals – Advisory Committee/Board Member, Consultant, Transport, Fees.. Janssen – Advisory Committee/Board Member, Consultant, Transport, Fees.. Medac – Advisory Committee/Board Member, Consultant, Transport or Fees. Merck Sharp & Dohme – Advisory Committee/Board Member, Consultant, Transport, Fees.. Pfizer – Advisory Committee/Board Member, Consultant, Transport, Fees.. Prometheus – Advisory Committee/Board Member, Consultant, Transport, Fees.. Takeda – Advisory Committee/Board Member, Consultant, Transport, Fees.. Theradiag – Advisory Committee/Board Member, Consultant, Transport, Fees..
Jimmy Limdi: AbbVie – Consultant, Grant/Research Support, Speakers Bureau. Abivax – Consultant, Speakers Bureau. AlfaSigma – Consultant, Speakers Bureau. Biohit – Consultant, Speakers Bureau. Bristol Myers Squibb – Consultant, Speakers Bureau. Celltrion – Consultant, Speakers Bureau. Eli Lilly and Company – Consultant, Speakers Bureau. Ferring – Consultant, Speakers Bureau. Galapagos – Consultant, Grant/Research Support, Speakers Bureau. Johnson & Johnson – Advisor or Review Panel Member, Speakers Bureau. MSD – Consultant, Speakers Bureau. Pfizer – Consultant, Speakers Bureau. Takeda – Consultant, Grant/Research Support, Speakers Bureau.
Radoslaw Kempinski: AbbVie – Lecture fees. Aboca S.p.A. Società Agricola – Lecture fees. Eli Lilly and Company – Lecture fees. Ferring – Lecture fees. Takeda – Grant/Research Support.
James D. Lewis: AbbVie – Grant/Research Support. Amgen – Advisory Committee/Board Member, Consultant, Data monitoring committee. Crohn’s & Colitis Foundation – Advisory Committee/Board Member, Consultant, Data monitoring committee. Dark Canyon Labs – Stock Options. Eli Lilly and Company – Advisory Committee/Board Member, Consultant, Grant/Research Support, Data monitoring committee. Galapagos – Advisory Committee/Board Member, Consultant, Data monitoring committee. Janssen Pharmaceuticals (Johnson & Johnson) – Advisory Committee/Board Member, Consultant, Grant/Research Support, Data monitoring committee, Educational grant. Merck – Advisory Committee/Board Member, Consultant, Data monitoring committee. Nestle Health Science – Grant/Research Support. Odyssey Therapeutics – Advisory Committee/Board Member, Consultant, Data monitoring committee. Pfizer – Advisory Committee/Board Member, Consultant, Data monitoring committee. Protagonist Therapeutics – Advisory Committee/Board Member, Consultant, Data monitoring committee. Sanofi – Advisory Committee/Board Member, Consultant, Data monitoring committee. Spyre Pharmaceuticals – Advisory Committee/Board Member, Consultant, Data monitoring committee. Takeda – Grant/Research Support.
Erica Cohen: AbbVie – Speakers Bureau. Eli Lilly and Company – Speakers Bureau. Janssen – Speakers Bureau. Pfizer – Advisory Committee/Board Member, Consultant. PRIME Education – Advisory Committee/Board Member, Consultant. Takeda – Advisory Committee/Board Member, Consultant, Speakers Bureau.
Karla Alaka: Eli Lilly and Company – Employee, Stock Options.
William Eastman: Eli Lilly and Company – Employee, Stock Options.
Tian Tian: Eli Lilly and Company – Employee, Stock Options.
Isabel Redondo: Eli Lilly and Company – Employee, Stock Options.
David Rubin: AbbVie – Advisory Committee/Board Member, Consultant, Speaker fees. Abivax SA – Consultant. Altrubio – Advisory Committee/Board Member, Consultant, Speaker feees, Stock Options. Avalo – Advisory Committee/Board Member, Consultant, Speaker fees. Bausch Health – Consultant. Bristol Myers Squibb – Advisory Committee/Board Member, Consultant, Speaker fees. Buhlmann Diagnostics – Advisory Committee/Board Member, Consultant, Speaker fees. Celltrion – Consultant. ClostraBio – Consultant. Connect BioPharma – Consultant. Cornerstones Health, Inc – Board of Directors membership. Douglas Pharmaceuticals – Consultant. Eli Lilly & Co. – Consultant. Foresee, Genentech (Roche) Inc. – Consultant. Image Analysis Group – Consultant. InDex Pharmaceutical – Consultant. Intouch Group – Advisory Committee/Board Member, Consultant, Speaker fees. Iterative Health – Advisory Committee/Board Member, Consultant, Speaker fees. Iterative Health – Stock Options. Janssen Pharmaceuticals – Consultant. Lilly – Advisory Committee/Board Member, Consultant, Speaker fees. Odyssey Therapeutics – Consultant. Pfizer – Advisory Committee/Board Member, Consultant, Speaker fees. Sanofi – Consultant. Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speaker fees. Throne – Consultant. Vedanta – Consultant.
Marla Dubinsky: AbbVie – Consultant, Grant/Research Support. Arena – Consultant. Astra Zeneca – Consultant. Boehringer Ingelheim – Consultant. Celgene – Consultant. Eli Lilly – Consultant. Gilead – Consultant. Janssen – Consultant, Grant/Research Support. Merck – Consultant. Pfizer – Consultant. Prometheus Laboratories – Consultant, Grant/Research Support. Sanofi – Consultant. Spyre – Consultant. Takeda – Consultant. Trellus Health – Stock Options, Stock-publicly held company(excluding mutual/index funds). UCB – Consultant.

Silvio Danese, MD, PhD¹, Axel Dignass, MD, PhD², David Laharie, ³, Jimmy Limdi, MD⁴, Radoslaw Kempinski, MD, PhD⁵, James D. Lewis, MD⁶, Erica R. Cohen, MD⁷, Karla Alaka, ⁸, William J. Eastman, ⁸, Tian Tian, ⁸, Isabel Redondo, MD⁸, David T. Rubin, MD⁹, Marla C. Dubinsky, MD¹⁰. P1069 - Mirikizumab Improves Bowel Urgency and Correlates With Patient-Reported Outcomes in Moderately-to-Severely Active Ulcerative Colitis: LUCENT-URGE Trial, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.