S0682 Absence of Bowel Urgency Is Associated With Significantly Improved Inflammatory Bowel Disease Related Quality of Life in a Phase 2 Trial of Mirikizumab in Patients With Ulcerative Colitis

Abstract

INTRODUCTION: Mirikizumab (miri), a humanized monoclonal antibody directed against the p19 subunit of IL-23, demonstrated efficacy and was well-tolerated in a phase 2 randomized clinical trial in patients with ulcerative colitis (UC). Bowel urgency is one of the most bothersome symptoms experienced by patients with UC and is closely tied to health-related quality of life (QoL). Here we show the relationship between patient-reported urgency and Inflammatory Bowel Disease Questionnaire (IBDQ) scores. METHODS: Patients (N = 247) were randomized 1:1:1:1 to receive intravenous placebo, miri 50 mg or 200 mg with possibility of exposure-based dose increases, or fixed miri 600 mg every 4 weeks. Patients who achieved clinical response at Week 12 (decrease in 9-point Mayo score ≥2 points and ≥35% from baseline [BL], and either a decrease in rectal bleeding [RB] subscore ≥1 or RB subscore of 0 or 1; n = 106) were re-randomized 1:1 to double-blind maintenance treatment with miri 200 mg subcutaneously every 4 or 12 weeks and were treated through Week 52. Absence of urgency at Weeks 12 and 52 was defined as having no urgency for the three consecutive days prior to each scheduled visit, regardless of urgency status at BL. Patients lacking urgency data were imputed as having experienced urgency at that visit. The mean change from BL (Week 0) in IBDQ scores between patients with absence or presence of urgency at Weeks 12 and 52 was determined using analysis of covariance models. RESULTS: As previously reported, miri significantly reduced urgency over 52 weeks of treatment (1). In this analysis, total IBDQ score was significantly higher in patients with absence of urgency compared to those with presence of urgency at weeks 12 and 52. [LSM (SE)]: Week 12, 179.2 (3.6) absence, 150.5 (3.2) presence, P < 0.0001; Week 52, 186.0 (3.91) absence, 163.1 (4.35) presence, P < 0.0001. A similar pattern was observed for the 4 IBDQ subscores and corresponded to percent changes from BL (% ΔBL) that were more than two times greater in patients with absence of urgency compared to patients with presence of urgency (Table 1). CONCLUSION: In patients with absence of urgency at Weeks 12 and 52, Qol as measured by IBDQ was significantly improved compared to those with urgency. Our data demonstrate the significant negative impact of urgency on QoL in patients with UC.Table 1