S1466 A Post-Hoc Analysis of the VARSITY Trial Assessing Outcomes in Mild-to-Moderate Ulcerative Colitis With Histologic Activity and MES 1

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]. Conclusion: 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.