S1628 Mirikizumab Demonstrates Long-Term Efficacy on Histological Resolution in the Phase 3, Multicenter, Open-Label VIVID-2 Extension Study

Introduction: VIVID-1 evaluated systematically obtained biopsies from 5 intestinal segments demonstrating that histologic (histo) readouts were impacted upon treatment with mirikizumab (MIRI). Methods: VIVID-2, the long-term extension study of VIVID-1, examines histo and combined endoscopic(endo)-histo endpoints at Week(W)104. These data are presented, as is the impact of 1-year(yr) histo response (H-res) and histo remission (H-rem) on endoscopic and clinical outcomes after 2 yrs of MIRI treatment. In VIVID-1, the MIRI group received induction with 900 mg intravenously (IV) at W0, 4, and 8, then 300 mg subcutaneously (SC) every 4W. W52 patients (pts) in endo response (E-res; ≥50% reduction from baseline in Simple Endoscopic Score for CD) continued the same MIRI SC dosing in VIVID-2. Endo non-responders received reinduction with MIRI IV at the start of VIVID-2 followed by SC dosing (IV-SC) as described. Two specimens from each of 5 intestinal segments (1 ileal, 4 colonic) were obtained from the edge of ulcers, or the most inflamed mucosa from randomized pts at screening, W12, W52 (VIVID-1), and W104 (W52 of VIVID-2). H-res: absence of epithelial neutrophils and epithelial damage, erosions, and ulceration or ≥50% decrease in either the active Robarts Histopathology Index or the active Global Histology Activity Score. H-rem: absence of mucosal neutrophils, no epithelial damage, and no erosions and ulcers. The criteria for H-res and H-rem had to be met in all 5 segments. Results: Among pts in E-res at W52 of VIVID-1: 81.2% maintained H-res and 57.5% maintained H-rem after an additional 52 weeks of MIRI SC treatment, 70.8% maintained combined endo-histo response. Interestingly, 25.6% pts who were in H-Res, but not in E-res at W52 of VIVID-1 maintained H-res and gained E-res during the 2nd year of MIRI treatment (IV-SC). In the overall MIRI-treated population (SC-SC and IV-SC), both H-res and H-rem were significantly associated with E-res (P < 0.001) and endo-remission (P < 0.001) at W104 while associations with Crohn’s Disease Activity Index remission (P = 0.313 and P = 0.771, respectively) and bowel urgency remission (P = 0.122 and P = 0.517, respectively) were not identified. Conclusion: In VIVID-2, achievement of histologic response and remission after 1 yr of miri treatment was strongly associated with longer term endoscopic outcomes. High rates of histologic and combined endo-histo endpoints were maintained after 2 yrs of treatment.