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Monday Poster Session

Category: IBD

P2670 - Effects of Mirikizumab and Ustekinumab on Histologic Inflammation Evaluated by Comprehensive Assessment in 5 Intestinal Segments in a Randomized Controlled Phase 3 Trial of Participants With Crohn’s Disease

Monday, October 28, 2024
10:30 AM – 4:00 PM ET
Location: Exhibit Hall E
Has Audio
Vipul Jairath, MBChB1, Fernando Magro, 2, Gert De Hertogh, 3, Brian G.. Feagan, MD1, Noam Harpaz, 4, Tadakazu Hisamatsu, MD, PhD5, Geert R. D'Haens, MD, PhD6, Rish Pai, MD, PhD7, Zhantao Lin, PhD8, Nathan Morris, 8, Marijana Protic, 8, Emily Hon, 8, Charles C. Owen, MD, MBA8, Rodrigo Escobar, 8, Walter Reinisch, MD, PhD9
1Western University, London, ON, Canada; 2Centro Hospitalar São João, Porto, Porto, Portugal; 3Laboratory of Translational Cell and Tissue Research, Leuven, Brabant Wallon, Belgium; 4Icahn School of Medicine at Mount Sinai, Mount Sinai, NY; 5Kyorin University School of Medicine, Tokyo, Tokyo, Japan; 6Amsterdam University Medical Center, Amsterdam, Limburg, Netherlands; 7Mayo Clinic, Scottsdale, AZ; 8Eli Lilly and Company, Indianapolis, IN; 9Medical University of Vienna, Vienna, Wien, Austria

Introduction: Responsiveness of histologic inflammation and of combined endoscopic-histologic endpoints to treatment are evolving measures of disease activity in Crohn’s Disease (CD). Mirikizumab (MIRI) increased histologic response (H-Res) and remission (H-Rem) relative to placebo (PBO) in the Phase 2 SERENITY trial.

Methods: This study evaluated the impact of MIRI and ustekinumab (USTE) on H-Res and H-Rem and combined endoscopic-histologic response (EH-Res) and remission (EH-Rem) in all patients (pts), pts with prior biologic failure (BF), pts without prior BF in moderately to severely active CD, in the randomized, double-blind, double-dummy, treat-through Phase 3 VIVID-1 trial. Two biopsy specimens from each of 5 intestinal segments (1 ileal and 4 colonic) were obtained from the edge of the ulcers, or the most inflamed mucosa from randomized pts at screening, and weeks (W)12, and 52. Criteria for H-Res: absence of epithelial neutrophils and epithelial damage, erosions and ulceration or ≥50% decrease in either the active Robarts Histopathology Index or the active Global Histologic Disease Activity Score. H-Rem: complete absence of mucosal neutrophils (in epithelium and lamina propria), and no epithelial damage, erosions and ulcers; these criteria had to be met in all biopsy specimens. Endoscopic response: ≥50% improvement from baseline in Simple Endoscopic Score for CD (SES-CD). Endoscopic remission: SES-CD total score ≤4 and ≥2-point reduction from baseline and no subscore >1 in any individual variable.

Results: At W52, nominally significant differences between MIRI and USTE were observed in achieving H-Res in all pts (p=.007) and in BF pts (p=.006). For EH-Res, differences of MIRI vs USTE were numerically greater but not statistically significant in all pts (p=.063) but were nominally significant among BF pts (p=.023). While numerical differences between MIRI and USTE were observed in H-Rem and EH-Rem in all pts (H-Rem: p=.685; EH-Rem: p=.363) and in BF pts (H-Rem: p=.365; EH-Rem: p=.237), no significant differences were observed in these endpoints (Table).



Discussion: Using strict definitions, all histology-based endpoints were achieved by MIRI vs PBO. For comparison vs USTE, MIRI also showed nominal statistical difference for H-Res, which was prespecified and is considered the most sensitive to change, particularly driven by BF pts. The implication of these results on clinical endpoints and long-term outcomes, including hospitalization rates and surgeries, requires further evaluation.


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.


Disclosures:
Vipul Jairath: AbbVie – Consultant, Grant/Research Support, Speakers Bureau. Alimentiv – Consultant, Employee, Grant/Research Support, Speakers Bureau. Arena Pharmaceuticals – Consultant, Grant/Research Support, Speakers Bureau. Asahi Kasei Pharma – Consultant, Grant/Research Support, Speakers Bureau. Asieris Pharmaceuticals – Consultant, Grant/Research Support, Speakers Bureau. AstraZeneca – Consultant, Grant/Research Support, Speakers Bureau. Avoro Capital – Advisory Committee/Board Member, Consultant. Bristol Myers Squibb – Consultant, Grant/Research Support, Speakers Bureau. Celltrion – Consultant, Grant/Research Support, Speakers Bureau. Eli Lilly and Company – Consultant, Grant/Research Support, Speakers Bureau. Endpoint Health – Advisory Committee/Board Member, Consultant. Enthera – Advisory Committee/Board Member, Consultant. Ferring Pharmaceuticals – Consultant, Grant/Research Support, Speakers Bureau. Flagship Pioneering – Consultant, Grant/Research Support, Speakers Bureau. Fresenius Kabi – Consultant, Grant/Research Support, Speakers Bureau. Galapagos NV – Consultant, Grant/Research Support, Speakers Bureau. Genentech – Consultant, Grant/Research Support, Speakers Bureau. Gilde Healthcare – Advisory Committee/Board Member, Consultant. Gilead Sciences – Consultant, Grant/Research Support, Speakers Bureau. GlaxoSmithKline – Consultant, Grant/Research Support, Speakers Bureau. Innomar – Advisory Committee/Board Member, Consultant. JAMP – Advisory Committee/Board Member, Consultant. Janssen – Consultant, Grant/Research Support, Speakers Bureau. London Health Sciences Centre – Employee. Merck – Consultant, Grant/Research Support, Speakers Bureau. Metacrine – Consultant, Grant/Research Support, Speakers Bureau. Mylan – Consultant, Grant/Research Support, Speakers Bureau. Pandion Therapeutics – Consultant, Grant/Research Support, Speakers Bureau. Pendopharm – Consultant, Grant/Research Support, Speakers Bureau. Pfizer – Consultant, Grant/Research Support, Speakers Bureau. Prometheus Therapeutics and Diagnostics – Consultant, Grant/Research Support, Speakers Bureau. Protagonist Therapeutics – Consultant, Grant/Research Support, Speakers Bureau. Reistone Biopharma – Consultant, Grant/Research Support, Speakers Bureau. Roche – Consultant, Grant/Research Support, Speakers Bureau. Roivant – Advisory Committee/Board Member, Consultant. Sandoz – Consultant, Grant/Research Support, Speakers Bureau. SCOPE – Advisory Committee/Board Member, Consultant. Second Genome – Consultant, Grant/Research Support, Speakers Bureau. Shire – Speakers Bureau. Sorriso Pharmaceuticals – Consultant, Grant/Research Support, Speakers Bureau. Synedgen – Advisory Committee/Board Member, Consultant. Takeda – Consultant, Grant/Research Support, Speakers Bureau. TD Securities – Advisory Committee/Board Member, Consultant. Teva – Consultant, Grant/Research Support, Speakers Bureau. Topivert – Consultant, Grant/Research Support, Speakers Bureau. Ventyx Biosciences – Consultant, Grant/Research Support, Speakers Bureau. Vividion Therapeutics – Consultant, Grant/Research Support, Speakers Bureau.
Fernando Magro: AbbVie – Received honoraria, Speakers Bureau. Biogen – Received honoraria, Speakers Bureau. Dr. Falk Pharma – Received honoraria. Ferring Pharmaceuticals – Received honoraria, Speakers Bureau. Hospira – Received honoraria, Speakers Bureau. Laboratórios Vitória – Received honoraria, Speakers Bureau. Merck Sharp & Dohme – Received honoraria, Speakers Bureau. Vifor Pharma – Received honoraria, Speakers Bureau.
Gert De Hertogh: Centocor Inc. – Fees for clinical trial activities (paid to his institution). Johnson & Johnson – Fees for clinical trial activities (paid to his institution).
Brian Feagan: AbbVie – Advisory Committee/Board Member, Consultant, Speakers Bureau. AbolerIS – Consultant. AgomAB Therapeutics – Consultant. Allianthera – Consultant. Amgen – Advisory Committee/Board Member, Consultant. AnaptysBio – Advisory Committee/Board Member, Consultant. Applied Molecular Transport Inc – Advisory Committee/Board Member, Consultant. Arena Pharma – Consultant. Atomwise – Consultant. Avoro Capital Advisors – Consultant. Axio Research – Advisory Committee/Board Member. BioJamp – Consultant. Biora Therapeutics – Consultant. Boehringer Ingelheim – Advisory Committee/Board Member, Consultant. Boxer – Consultant. Celgene/Bristol Myers Squibb – Advisory Committee/Board Member, Consultant. Celsius Therapeutics – Consultant. Connect BioPharma – Consultant, stock or other ownership interest. Cytoki – Consultant. Disc Medicine – Consultant. Duality – Consultant. EcoR1 Capital – Advisory Committee/Board Member, Consultant. Equillium – Consultant. Ermium – Consultant. First Wave – Consultant. First Word Group – Consultant. Galapagos – Consultant. Galen Atlantica – Consultant. Genentech/Roche – Advisory Committee/Board Member, Consultant. Gilead – Consultant. GlaxoSmithKline – Advisory Committee/Board Member, Consultant. Gossamer Pharma – Consultant, Stock Options. Hinge Bio – Consultant. Hot Spot Therapeutics – Consultant. Imhotex – Consultant. Immunic Therapeutics – Consultant. InDex Pharmaceuticals – Advisory Committee/Board Member, Consultant. JAKAcademy – Consultant. Janssen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Japan Tobacco Inc. – Consultant. Kaleido Biosciences – Consultant. L.E.K. Consulting – Consultant. Landos Biopharma – Consultant. Leadiant – Consultant. Lenczner Slaght – Consultant, payment for expert testimony. LifeSci Capital – Consultant. Lilly – Advisory Committee/Board Member, Consultant. Lument AB – Consultant. Millennium – Consultant. MiroBio – Advisory Committee/Board Member, Consultant. Morgan Lewis – Consultant, payment for expert testimony. Morphic Therapeutics – Advisory Committee/Board Member, Consultant. Mylan – Consultant. OM Pharma – Consultant. Origo BioPharma – Advisory Committee/Board Member, Consultant. Orphagen – Consultant. Pandion Therapeutics – Consultant. Pendopharm – Consultant. Pfizer Inc – Advisory Committee/Board Member, Consultant, Grant/Research Support. Play to Know AG – Consultant. Progenity – Advisory Committee/Board Member, Consultant. Prometheus – Advisory Committee/Board Member, Consultant. Protagonist – Consultant. PTM Therapeutics – Consultant. Q32 Bio – Consultant. Rebiotix – Consultant. REDX – Advisory Committee/Board Member, Consultant. Roche – Consultant. Sandoz – Consultant. Sanofi – Advisory Committee/Board Member, Consultant. Seres Therapeutics – Consultant. Silverback Therapeutics – Consultant. Surrozen Inc. – Consultant. Takeda – Advisory Committee/Board Member, Consultant, Speakers Bureau. Teva – Advisory Committee/Board Member, Consultant. Thelium – Consultant. Tigenix – Consultant. Tillotts Pharma – Advisory Committee/Board Member, Consultant. Ventyx Biosciences – Consultant. VHSquared Ltd – Consultant. Viatris – Consultant. Ysios – Consultant. Ysopia – Consultant. Zealand Pharma – Consultant.
Noam Harpaz: AbbVie – Advisory Committee/Board Member, Consultant. Bristol Meyers Squibb – Advisory Committee/Board Member, Consultant. Eli Lilly and Company – Advisory Committee/Board Member, Consultant. PathAI Inc. – Advisory Committee/Board Member, Consultant.
Tadakazu Hisamatsu: AbbVie – Grant/Research Support, lecture fees. Bristol Myers Squibb – Consultant. Daiichi-Sankyo – Grant/Research Support. EA Pharma – Consultant, Grant/Research Support, lecture fees. Gilead Sciences – Consultant. Janssen – Consultant. JIMRO – Grant/Research Support. Mitsubishi Tanabe Pharma Corporation – Grant/Research Support, lecture fees. Mochida Pharmaceutical – Grant/Research Support. Nippon Kayaku – Grant/Research Support. Pfizer – Grant/Research Support. Takeda Pharmaceutical – Grant/Research Support, lecture fees.
Geert D'Haens: AbbVie – Advisor or Review Panel Member, Speakers Bureau. Agomab Therapeutics – Advisor or Review Panel Member. Alimentiv – Advisor or Review Panel Member. Allergan – Advisor or Review Panel Member. Alphabiomics – Advisor or Review Panel Member. AstraZeneca – Advisor or Review Panel Member. Boehringer Ingelheim – Advisor or Review Panel Member. Bristol Myers Squibb – Advisor or Review Panel Member, Speakers Bureau. Celltrion – Advisor or Review Panel Member, Grant/Research Support. Eli Lilly – Advisor or Review Panel Member, Speakers Bureau. Ferring – Advisor or Review Panel Member. Galapagos – Advisor or Review Panel Member, Speakers Bureau. GlaxoSmithKline – Advisor or Review Panel Member. Immunic – Advisor or Review Panel Member. Johnson & Johnson – Advisor or Review Panel Member, Speakers Bureau. Pfizer Inc – Advisor or Review Panel Member, Grant/Research Support, Speakers Bureau. Seres – Advisor or Review Panel Member. Takeda – Advisor or Review Panel Member, Speakers Bureau. Tillotts – Advisor or Review Panel Member, Speakers Bureau. Ventyx – Advisor or Review Panel Member.
Rish Pai: AbbVie – Consultant. Alimentiv – Consultant. Allergan – Consultant. Eli Lilly and Company – Consultant. Genentech – Consultant. PathAI – Consultant.
Zhantao Lin: Eli Lilly and Company – Employee, Stock Options.
Nathan Morris: Eli Lilly and Company – Employee, Stock Options.
Marijana Protic: Eli Lilly and Company – Employee, Stock Options.
Emily Hon: Eli Lilly and Company – Employee, Stock Options.
Charles C. Owen: Eli Lilly and Company – Employee, Stock Options.
Rodrigo Escobar: Eli Lilly and Company – Employee, Stock Options.
Walter Reinisch: AbbVie – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Amgen – Advisory Committee/Board Member, Consultant. AOP Orphan – Consultant. Boehringer Ingelheim – Advisory Committee/Board Member, Consultant. Bristol Myers Squibb – Advisory Committee/Board Member, Consultant. Calyx – Consultant. Celltrion – Advisory Committee/Board Member, Consultant, Speakers Bureau. Eli Lilly – Consultant. Ferring – Speakers Bureau. Galapagos – Advisory Committee/Board Member, Consultant, Speakers Bureau. Gilead – Consultant. Index Pharma – Consultant. Janssen – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Medahead – Consultant. Microbiotica – Consultant. MSD – Speakers Bureau. Pfizer – Advisory Committee/Board Member, Consultant, Speakers Bureau. Roche – Speakers Bureau. Sandoz – Grant/Research Support. Sanofi – Grant/Research Support. Sobi – Speakers Bureau. Takeda – Consultant, Grant/Research Support, Speakers Bureau.


Vipul Jairath, MBChB1, Fernando Magro, 2, Gert De Hertogh, 3, Brian G.. Feagan, MD1, Noam Harpaz, 4, Tadakazu Hisamatsu, MD, PhD5, Geert R. D'Haens, MD, PhD6, Rish Pai, MD, PhD7, Zhantao Lin, PhD8, Nathan Morris, 8, Marijana Protic, 8, Emily Hon, 8, Charles C. Owen, MD, MBA8, Rodrigo Escobar, 8, Walter Reinisch, MD, PhD9. P2670 - Effects of Mirikizumab and Ustekinumab on Histologic Inflammation Evaluated by Comprehensive Assessment in 5 Intestinal Segments in a Randomized Controlled Phase 3 Trial of Participants With Crohn’s Disease, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.