S0683 Absence of Bowel Urgency Is Associated With Improvements in Clinical Outcomes in Patients With Ulcerative Colitis Receiving Mirikizumab

Abstract

INTRODUCTION: Bowel urgency is one of the most common yet often overlooked symptoms experienced by patients with UC (1). Mirikizumab (miri), a humanized monoclonal antibody directed against the p19 subunit of IL-23, demonstrated efficacy (2), was well-tolerated, and significantly reduced urgency (3) in a phase 2 randomized clinical trial in patients with ulcerative colitis (UC). Here we show the relationship between patient-reported urgency and improvements in measures of clinical efficacy. METHODS: Patients (N = 249) were randomized 1:1:1:1 to receive intravenous placebo, miri 50mg or 200mg with possibility of exposure-based dose increases, or fixed miri 600 mg every 4 weeks. Patients who achieved clinical response (n = 106) at Week 12 were re-randomized 1:1 to double-blind maintenance treatment with miri 200 mg subcutaneously every 4 or 12 weeks and treated through Week 52. Analyses of the association between urgency and clinical efficacy at Weeks 12 and 52 were conducted by pooling treatment arms in the induction and maintenance periods, respectively. Absence of urgency was defined as reporting no urgency for the three consecutive days prior to each scheduled visit, regardless of urgency status at BL. Patients with missing urgency data were imputed as having experienced urgency at that visit. Clinical efficacy in patients with presence or absence of urgency was compared using logistic regression models adjusting for geographic region, prior biologic experience, age, and sex. RESULTS: As previously reported, miri significantly reduced urgency over 52 weeks of treatment (3). At Week 12 and Week 52, patients with absence of urgency had significantly higher rates of improvement on all clinical outcomes examined (clinical remission, clinical response, stool frequency (SF) remission, rectal bleeding (RB) remission, endoscopic remission, histologic remission, mucosal healing; see Table 1 for definitions and P values) compared to those with presence of urgency. CONCLUSION: Absence of urgency is strongly associated with improved clinical, endoscopic and histologic outcomes. These findings suggest that urgency may be a useful surrogate marker of disease activity and is a distinct symptom that is important to discuss with patients with UC.Table 1