Endoscopic and Histologic Remission After 2 Years Treatment With Mirikizumab in Patients With Moderately-to-Severely Active Ulcerative Colitis

Introduction: Mirikizumab (miri), a p19-directed IL-23 antibody, has shown efficacy in achieving clinical, endoscopic and histological response and remission after 52 weeks of therapy in patients with moderately-to-severely active ulcerative colitis (UC) in Phase 3 trials (LUCENT-1,; LUCENT-2). Histological healing in UC can indicate remission depth. Here, we report from LUCENT-3 the proportion of patients with and without prior biologic or tofacitinib failure who achieved histologic and endoscopic remission after 2 years of miri treatment. Methods: LUCENT-3 is an ongoing, single-arm, outpatient, multicenter, long-term extension Phase 3 study evaluating the efficacy and safety of miri in patients with moderately-to-severely active UC. All enrolled patients received open-label subcutaneous miri 200 mg every 4 weeks. This analysis focused on miri responders at Week (W)52 (patients who were responders at W12, were re-randomized to miri maintenance and were in response at the end of LUCENT-2) who were enrolled in the long-term extension and continued to receive miri for additional 52 weeks. Endpoints of interest are the proportions of patients with histologic improvement, endoscopic remission, endoscopic normalization, histologic-endoscopic mucosal improvement (HEMI), histologic-endoscopic mucosal remission (HEMR), and alternate HEMR (histologic remission and endoscopic normalization) at W104. P-values were calculated using Pearson chi-square test. Missing response data were imputed as non-response. Results: Among the Week 52 miri responders (N=239), 60.3% were male, with mean age of 43.9. Mean baseline modified Mayo Score was 6.7, and 33.5% had prior biologic or tofacitinib exposure. After 2 years of miri treatment, 65.3% patients achieved endoscopic remission and 51.9% achieved histologic remission. HEMI and HEMR were achieved by 53.1% and 47.7% of patients, respectively. A similar proportion of patients achieved histologic improvement, histologic remission, endoscopic remission, HEMI, and HEMR irrespective of prior biologic or tofacitinib failure, with only endoscopic normalization and alternate HEMR showing statistically significant higher rates for patients who didn´t have prior biologic or tofacitinib failure (Table 1). Conclusion: In LUCENT-3, sustained histologic and endoscopic remission were observed in patients with moderately-to-severely active UC who were treated with mirikizumab for 2 years, regardless of previous biologic or tofacitinib failure. Table 1. - Proportion of Patients with Histologic and Endoscopic Outcome at Week 104 by Prior Biologic or Tofacitinib Treatment Failure Status at Baseline Mirikizumab Response Rates at Week 104 Prior Biologic or Tofacitinib Not Failed (N=166) Prior Biologic or Tofacitinib Failed (N=73) Overall (N=239) Histologic improvement a 99 (59.6%) 43 (58.9%) 142 (59.4%) Histologic remission b 85 (51.2%) 39 (53.4%) 124 (51.9%) Endoscopic remission c 114 (68.7%) 42 (57.5%) 156 (65.3%) HEMI d 90 (54.2%) 37 (50.7%) 127 (53.1%) HEMR e 80 (48.2%) 34 (46.6%) 114 (47.7%) Endoscopic normalization f 56 (33.7%) 13 (17.8%) * 69 (28.9%) Alternate HEMR g 48 (28.9%) 11 (15.1%) * 59 (24.7%) Data presented as n (%); P-value, *P< 0.05. Abbreviations: ES = Endoscopic Subscore; HEMI = Histologic Endoscopic Mucosal Improvement; HEMR = Histologic Endoscopic Mucosal Remission.aGeboes score≤3.1.bGeboes score≤2B.0.cES=0 or 1, excluding friability.dGeboes score≤3.1 and ES=0 or 1, excluding friability.eGeboes score≤2B.0 and ES=0 or 1, excluding friability.fES=0.gES=0 and Geboes score≤2B.0.