Patients with ulcerative colitis that have endoscopic Mayo score 1 and active histologic inflammation have similar outcomes to mild-moderate patients with Mayo score 2: a post hoc analysis of the VARSITY trial

Background Mild-moderate ulcerative colitis (UC) in clinical trials has been defined as an adapted Mayo Clinic score ≥4 with a Mayo endoscopic score (MES) of 2 and rectal bleeding score ≥1. This study aims to explore whether UC patients with lower endoscopic burden but active histology have similar outcomes to those with ‘conventional’ mild-moderate UC. Methods This was a post hoc analysis from the treat-through VARSITY study (Clinicaltrial.gov: NCT02497469). Patients who completed induction (at week 14) with mild-moderate UC based on the conventional definition were compared to patients with histologically active MES 1 for achieving histo-endoscopic mucosal improvement (HEMI) at week 52, defined as MES ≤ 1 and Geboes highest grade <3.2. Secondary outcomes included endoscopic remission (ER) (MES = 0), histologic improvement (Geboes highest grade <3.2), and clinical remission (CR) (total Mayo score ≤2 and no subscore >1). Histologically active disease was defined as Geboes highest grade >3.2 (>50% of neutrophil crypt involvement in the epithelium). Results Week 52 outcomes were similar among patients with mild-moderate UC compared to those with histologically active disease and MES of 1. At week 52, a similar proportion of patients achieved HEMI [19/79 (24.1%) vs. 28/113 (24.8%), P = 0.908], ER [23/79 (29.1%) vs. 35/113 (31.0%), P = 0.782], histologic improvement [23/79 (29.1%) vs. 36/113 (31.9%), P = 0.685], and CR [38/79 (48.1%) vs. 66/113 (58.4%), P = 0.158]. Conclusions Patients with histologically active MES 1 had comparable clinical and histologic outcomes at week 52 as those with conventional mild-moderate UC, suggesting that histology may better predict prognosis than symptoms or endoscopy alone.