S752 Biomarkers and Bowel Urgency in Response to Mirikizumab for Ulcerative Colitis

Abstract

Introduction: Mirikizumab (miri), a p19-directed IL-23 antibody, significantly reduced bowel urgency1 in a phase 2 randomized clinical trial in pts with ulcerative colitis (UC). We explore relationships between patient-reported urgency and inflammatory biomarkers C-reactive protein (CRP) and fecal calprotectin (fCLP). Methods: Pts (N=249) were randomized 1:1:1:1 to receive intravenous PBO, 50 or 200mg miri with exposure-based dose increase possibility or fixed miri 600mg every 4weeks (W). Pts achieving clinical response (n=106) at W12 were re-randomized 1:1 into double-blind maintenance with miri 200mg subcutaneously every 4 or 12W through W52. Association between urgency and biomarkers at W12 and W52 was analyzed by pooling treatment arms in induction and maintenance periods, respectively. Absence of urgency was defined as no urgency reported for 3 consecutive days prior to each scheduled visit, regardless of urgency status at baseline (BL). Pts with missing urgency data were imputed as having experienced urgency at that visit. Biomarker levels were summarized with descriptive statistics. Reduction from BL (ΔBL;LS mean±SE) in biomarker levels was compared in pts with presence or absence of urgency by ANCOVA models with covariates: baseline biomarker value, urgency status, geographic region, prior biologic experience, age, gender. Results: At W12, pts with absence of urgency had significantly greater ΔBL in CRP and fCLP compared to pts with presence of urgency(CRP mg/L: no urgency group(NUG) -7(1.6); urgency group(UG) 3(1.5), p=0.025; fCLP µg/g: NUG -1614(416); UG -109(388),p=0.003. At W52, there was no statistically significant difference in ΔBL in CRP or fCLP between pts with absence or presence of urgency, but levels of CRP and fCLP continued to decrease from W12 to W52. The ΔBL at W52 was greater in presence than absence of urgency group in this responder population (Table1). Conclusion: Absence of urgency at W12 is strongly associated with reduced levels of CRP and fCLP suggesting reduction in colonic inflammation associated with absence of urgency. Among pts who responded to induction therapy, biomarker levels continued to decrease regardless of bowel urgency. Hence, urgency in maintenance phase may be associated with other factors.Table 1.: Efficacy Endpoints at Weeks 1, 2, and 3