P1027 - A Post-Hoc Analysis of the VARSITY Trial Assessing Outcomes in Mild-to-Moderate Ulcerative Colitis With Histologic Activity and MES 1

Nazmus Khan, BSc(Hons), MBChB¹, Emily Wong, ¹, Neeraj Narula, MD¹, John K. Marshall, MSc, MD, BA², Parambir S. Dulai, MD³, Walter Reinisch, MD, PhD⁴, Vipul Jairath, MBChB, DPhil, MRCP⁵
1McMaster University, Hamilton, ON, Canada; 2Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada, Hamilton, ON, Canada; 3Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL; 4Medical University of Vienna, Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Spitalgasse, Wien, Austria; 5Department of Medicine and Department of Epidemiology and Biostatistics, Western University, London, ON, Canada

Introduction: Mild-to-moderate ulcerative colitis (UC) is traditionally defined by a total Mayo Clinic score ≥4, a Mayo Endoscopic Score (MES) of 2, and a Rectal Bleeding Score (RBS) ≥1. Endoscopic improvement has conventionally included both MES 0 and 1, yet studies indicate differing relapse risks, with MES 1 associated with poorer long-term outcomes. Importantly, patients with MES 1 and ongoing histologic inflammation are often excluded from clinical trials, limiting understanding of their disease trajectory and therapeutic needs.

Methods: This post-hoc analysis utilized data from the VARSITY trial. Patients who met the conventional definition of mild-to-moderate UC at week 14 were compared to those with MES 1 and active histology. The primary endpoint was histo-endoscopic mucosal improvement (HEMI) at week 52, defined as MES ≤1 and Geboes score < 3.2. Secondary outcomes included endoscopic remission (MES 0), histologic improvement (Geboes < 3.2), and clinical remission (total Mayo ≤2 with no subscore >1). Histologic activity was defined as Geboes >3.2.

Results: At week 52, both groups showed comparable rates of HEMI [24.1% (19/79) vs. 24.8% (28/113); p=0.908], endoscopic remission [29.1% vs. 31.0%; p=0.782], histologic improvement [29.1% vs. 31.9%; p=0.685], and clinical remission [48.1% vs. 58.4%; p=0.158].

Discussion: Patients with MES 1 and histologic activity appear to experience similar outcomes to those with mild-to-moderate disease by conventional criteria. These findings challenge current assumptions around disease severity and emphasize the importance of tailoring treatment decisions based on a more nuanced understanding of mucosal and histologic activity. Incorporating histologic assessment into routine practice may improve individualized care and optimize long-term outcomes. Further prospective studies are needed to validate these findings and to better define optimal management strategies for this patient subgroup.

Disclosures:
Nazmus Khan indicated no relevant financial relationships.
Emily Wong indicated no relevant financial relationships.
Neeraj Narula: Abbvie – Advisory Committee/Board Member, Consultant. Amgen – Advisory Committee/Board Member, Consultant. Eli Lilly – Advisory Committee/Board Member, Consultant. Ferring – Advisory Committee/Board Member, Consultant. Fresinius Kabi – Advisory Committee/Board Member, Consultant. Innomar Strategies – Advisory Committee/Board Member, Consultant. Iterative Health – Advisory Committee/Board Member, Consultant. Janssen – Advisory Committee/Board Member, Consultant. Novartis – Advisory Committee/Board Member, Consultant. Organon – Advisory Committee/Board Member, Consultant. Pfizer – Advisory Committee/Board Member, Consultant. Sandoz – Advisory Committee/Board Member, Consultant. Takeda – Advisory Committee/Board Member, Consultant.
John Marshall: AbbVie – Advisory Committee/Board Member, Speakers Bureau. Alimentiv – Advisory Committee/Board Member. Amgen – Advisory Committee/Board Member, Speakers Bureau. AstraZeneca – Advisory Committee/Board Member. Bausch Health – Advisory Committee/Board Member, Speakers Bureau. Bristol Myers Squibb – Advisory Committee/Board Member. Celltrion – Advisory Committee/Board Member. Ferring – Advisory Committee/Board Member, Speakers Bureau. Fresenius Kabi – Advisory Committee/Board Member, Speakers Bureau. Janssen – Advisory Committee/Board Member, Speakers Bureau. Lilly – Advisory Committee/Board Member. Lupin – Advisory Committee/Board Member. Organon – Advisory Committee/Board Member, Speakers Bureau. Paladin – Advisory Committee/Board Member. Pfizer Inc – Advisory Committee/Board Member, Speakers Bureau. Pharmascience – Advisory Committee/Board Member, Speakers Bureau. Qu Biologics – Advisory Committee/Board Member. Roche – Advisory Committee/Board Member, Speakers Bureau. Sandoz – Advisory Committee/Board Member. SCOPE – Advisory Committee/Board Member. Takeda – Advisory Committee/Board Member, Speakers Bureau. Teva – Advisory Committee/Board Member. Viatris – Advisory Committee/Board Member, Speakers Bureau.
Parambir S. Dulai: AbbVie – Consultant. Abivax – Consultant. Adiso – Consultant. Alimentiv – Consultant. Bristol Myers Squibb – Consultant. Celltrion – Consultant. Digbi Health – Stock Options. Genentech – Consultant. Geneoscopy – Consultant. GSK – Consultant. Janssen – Consultant. Lilly – Consultant. Pfizer – Consultant, Grant/Research Support. Precidiag – Royalties. Takeda – Consultant, Grant/Research Support.
Walter Reinisch: AbbVie – Advisory Committee/Board Member, Consultant, Grant/Research Support. Actelion – Advisory Committee/Board Member, Consultant. Alpha Wasserman – Advisory Committee/Board Member, Consultant. AstraZeneca – Advisory Committee/Board Member, Consultant. Cellerix – Advisory Committee/Board Member, Consultant. Cosmo Pharmaceuticals – Advisory Committee/Board Member, Consultant. Ferring Pharmaceuticals – Advisory Committee/Board Member, Consultant. Genentech – Advisory Committee/Board Member, Consultant. Grunenthal – Advisory Committee/Board Member, Consultant. Johnson & Johnson – Advisory Committee/Board Member, Consultant. Merck – Advisory Committee/Board Member, Consultant. Millennium – Advisory Committee/Board Member, Consultant. Novo Nordisk – Advisory Committee/Board Member, Consultant. Nycomed – Advisory Committee/Board Member, Consultant. Pfizer – Advisory Committee/Board Member, Consultant. Pharmacosmos – Advisory Committee/Board Member, Consultant. Salix Pharmaceuticals – Advisory Committee/Board Member, Consultant. Schering-Plough – Advisory Committee/Board Member, Consultant. Takeda – Advisory Committee/Board Member, Consultant. UCB Pharma – Advisory Committee/Board Member, Consultant. Vifor Pharma – Advisory Committee/Board Member, Consultant.
Vipul Jairath: AbbVie – Consultant, Grant/Research Support, Speakers Bureau. Alimentiv – Consultant, Grant/Research Support. 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 – 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 – Consultant. Enthera – 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 – Consultant. Gilead Sciences – Consultant, Grant/Research Support, Speakers Bureau. GlaxoSmithKline – Consultant, Grant/Research Support, Speakers Bureau. Innomar – Consultant. JAMP – Consultant. Johnson & Johnson – Advisor or Review Panel Member, Speakers Bureau. 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 – Consultant. Sandoz – Consultant, Grant/Research Support, Speakers Bureau. Second Genome – Consultant, Grant/Research Support, Speakers Bureau. Shire – Speakers Bureau. Sorriso Pharmaceuticals – Consultant, Grant/Research Support, Speakers Bureau. Syndegen – Consultant. Takeda – Consultant, Intellectual Property/Patents, Speakers Bureau. TD Securities – 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.

Nazmus Khan, BSc(Hons), MBChB¹, Emily Wong, ¹, Neeraj Narula, MD¹, John K. Marshall, MSc, MD, BA², Parambir S. Dulai, MD³, Walter Reinisch, MD, PhD⁴, Vipul Jairath, MBChB, DPhil, MRCP⁵. P1027 - A Post-Hoc Analysis of the VARSITY Trial Assessing Outcomes in Mild-to-Moderate Ulcerative Colitis With Histologic Activity and MES 1, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.