Icahn School of Medicine at Mount Sinai New York, NY
Vipul Jairath, MBChB1, Bruce E.. Sands, MD, FACG2, Maria Chaparro, MD, PhD3, Minhu Chen, 4, Geert R. D'Haens, MD, PhD5, Marla C. Dubinsky, MD2, Marc Ferrante, MD, PhD6, Laurent Peyrin-Biroulet, MD, PhD7, Stefan Schreiber, MD8, Simon Travis, 9, Hilde Carlier, 10, Zhantao Lin, PhD10, Richard Moses, 10, Marijana Protic, 10, Aisha Vadhariya, 10, Konstantinos Tsilkos, 10, Subrata Ghosh, MD11 1Western University, London, ON, Canada; 2Icahn School of Medicine at Mount Sinai, New York, NY; 3Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigacíon Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Diego de León, Madrid, Spain; 4First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China; 5Amsterdam University Medical Center, Amsterdam, Limburg, Netherlands; 6University Hospitals, Leuven, Vlaams-Brabant, Belgium; 7INFINY Institute, FHU-CURE, INSERM NGERE, Nancy University Hospital, Vandœuvre-lès-Nancy, Lorraine, France; McGill University Health Centre, Montreal, QC, Canada, Nancy, Lorraine, France; 8University Hospital, Kiel, Schleswig-Holstein, Germany; 9University of Oxford, Oxford, England, United Kingdom; 10Eli Lilly and Company, Indianapolis, IN; 11University College Cork, Cork, Cork, Ireland
Introduction: Bowel urgency (BU), the sudden or immediate need to have a bowel movement, is an impactful symptom of Crohn’s disease (CD) that varies in intensity. We report the efficacy of the IL-23 p19 inhibitor, mirikizumab (miri) in improving BU among patients with moderately-to-severely active CD from the phase 3 VIVID-1 trial (NCT03926130). VIVID-1 co-primary and gated endpoints, including comparison with ustekinumab, are already reported.
Methods: Adult patients (N=1065) were randomised to placebo (PBO) or miri 900mg intravenously at weeks (W) 0, 4, and 8, then 300mg subcutaneously every 4 weeks (Q4W) from W12 to W52. At W12, PBO responders continued PBO to W52, non-responders received the blinded miri regimen per protocol. BU was assessed at W12 and W52 using the Urgency Numeric Rating Scale (UNRS). We evaluated the proportion of patients with baseline (BL) UNRS ≥3 and ≥6 who achieved BU Clinically Meaningful Improvement (CMI; >3 change in UNRS) and BU remission (UNRS ≤2). Treatment comparisons used Cochran-Mantel-Haenszel tests with non-responder imputation for missing values.
Results: Study population: 55.1% male. Mean (SD) age 36.2 (13.0) years. Disease duration 7.4 (7.9) years. At BL, median (Q1, Q3) UNRS 6.9 (5.2, 8.1), 94.5% patients achieved UNRS ≥3 and 66.0% patients achieved ≥6. In patients with BL UNRS ≥3, nominally significantly higher proportions of miri versus PBO patients achieved BU CMI and BU remission at both W12 and W52 (Table). A nominally significantly greater proportion of miri-treated patients achieved W52 BU CMI-composite and BU remission-composite (Table). Similar results were seen with BL UNRS ≥6.
Discussion: BU is one of the most unrecognised symptoms in patients with CD. Patients enrolled in VIVID-1 had high BU scores at BL. Compared to PBO-treated patients, miri-treated patients achieved nominally significantly higher rates of BU CMI and remission at W12 and W52.
Note: The table for this abstract can be viewed in the ePoster Gallery section of the ACG 2024 ePoster Site or in The American Journal of Gastroenterology's abstract supplement issue, both of which will be available starting October 27, 2024.
Laurent Peyrin-Biroulet: AbbVie – Grant/Research Support, Personal fees. Allergan – Personal Fees. Alma Bio Therapeutics – Personal Fees. Amgen – Personal Fees. Applied Molecular Transport – Personal Fees. Arena – Personal Fees. Biogen – Personal Fees. Boehringer Ingelheim – Personal Fees. Bristol Myers Squibb – Personal Fees. Celgene – Personal Fees. Celltrion – Personal Fees. CTMA – Stock Options. Enterome – Personal Fees. Enthera – Personal Fees. Ferring – Personal Fees. Fresenius Kabi – Personal Fees. Genentech – Personal Fees. Gilead – Personal Fees. Hikma – Personal Fees. InDex Pharmaceuticals – Personal Fees. Janssen – Personal Fees. Lilly – Personal Fees. MSD – Grant/Research Support, Personal Fees. Mylan – Personal Fees. Nestlé – Personal Fees. Norgine – Personal Fees. Oppilan Pharma – Personal Fees. OSE Immunotherapeutics – Personal Fees. Pfizer Inc – Personal Fees. Pharmacosmos – Fees. Samsung Bioepis – Personal Fees. Sandoz – Personal Fees. Sterna – Personal Fees. Sublimity Therapeutics – Personal Fees. Takeda – Grant/Research Support, Personal Fees. Tillotts – Personal Fees. Vifor – Personal Fees.
Stefan Schreiber: AbbVie – Consultant, Personal fees, Speakers Bureau. Amgen – Personal fees. Arena Pharmaceuticals – Consultant, Personal fees, Speakers Bureau. Biogen – Consultant, Personal fees, Speakers Bureau. Bristol Myers Squibb – Consultant, Personal fees, Speakers Bureau. Celgene – Consultant, Personal fees, Speakers Bureau. Celltrion – Consultant, Personal fees, Speakers Bureau. Eli Lilly and Company – Personal fees. Falk – Consultant, Personal fees, Speakers Bureau. Ferring Pharmaceuticals – Personal fees. Fresenius – Consultant, Personal fees, Speakers Bureau. Galapagos – Personal fees. Gilead – Consultant, Personal fees. Hikma Pharmaceuticals – Advisory Committee/Board Member, Consultant. I-MAB – Consultant, Personal fees. Janssen – Consultant, Personal fees, Speakers Bureau. Morphic – Personal fees. MSD – Consultant, Personal fees, Speakers Bureau. Mylan – Consultant, Personal fees. Novartis – Personal fees. Pfizer Inc – Consultant, Personal fees, Speakers Bureau. Protagonist – Consultant, Personal fees. Provention Bio – Consultant, Personal fees. Roche – Personal fees. Sandoz/Hexal – Personal fees. Shire – Personal fees. Takeda – Consultant, Personal fees, Speakers Bureau. Theravance Biopharma – Consultant, Personal fees. Ventyx – Consultant, Personal fees.
Simon Travis: AbbVie – Grant/Research Support. Buhlmann – Grant/Research Support. ECCO – Grant/Research Support. Eli Lilly and Company – Grant/Research Support. Ferring Pharmaceuticals – Grant/Research Support. International Organization for the Study of IBD – Grant/Research Support. Janssen – Grant/Research Support. MSD – Grant/Research Support. Normal Collision Foundation – Grant/Research Support. Pfizer – Grant/Research Support. Procter & Gamble – Grant/Research Support. Schering-Plough – Grant/Research Support. Takeda – Grant/Research Support. UCB – Grant/Research Support. Vifor Pharma – Grant/Research Support. Warner Chilcott – Grant/Research Support.
Hilde Carlier: Eli Lilly and Company – Employee, Stock Options.
Zhantao Lin: Eli Lilly and Company – Employee, Stock Options.
Richard Moses: Eli Lilly and Company – Employee, Stock Options.
Marijana Protic: Eli Lilly and Company – Employee, Stock Options.
Aisha Vadhariya: Eli Lilly and Company – Employee, Stock Options.
Konstantinos Tsilkos: Eli Lilly and Company – Employee, Stock Options.