DOP107Mirikizumab provides positive histologic and endoscopic outcomes in patients with moderately to severely active Ulcerative Colitis

Abstract Background Mirikizumab (MIRI), an anti-IL-23p19 IgG4 monoclonal antibody, has demonstrated efficacy in treating patients with moderately to severely active ulcerative colitis (UC) and is effective in reducing colonic inflammation, as assessed by histologic and histologic-endoscopic outcomes. LUCENT-URGE (NCT05767021) was a Phase 3b, multicenter, open-label, single-arm study investigating bowel urgency (BU) and histologic features in patients with moderately-to-severely active ulcerative colitis (UC). Methods LUCENT-URGE enrolled 172 adult patients with a baseline Modified Mayo Score of 4-9 and with current bowel urgency (defined by Urgency Numeric Rating Scale (UNRS) ≥3). Patients received MIRI 300mg intravenously at Week (W)0, 4, and 8, followed by MIRI 200mg subcutaneously at W12, W16, W20, and W24. Up to 10 biopsy samples (5 from the colon and 5 from the rectum) were collected per endoscopy procedure. Histologic improvement was defined as a Geboes score ≤3.1: neutrophil infiltration in 5% of crypts; no crypt destruction; and no erosions, ulcerations, or granulation tissue. Histologic remission was defined as Geboes score ≤2B.0: no mucosal neutrophils, crypt destruction, erosions, ulcerations, or granulation tissue. Histologic endoscopic mucosal improvement (HEMI) was defined as Geboes score ≤3.1 and a Mayo endoscopic subscore (ES)=0 or 1​. Histologic endoscopic mucosal remission (HEMR) is defined as Geboes score ≤2B.0; ES = 0 or 1​. The percentage relative change for each element from W12 to W28 was calculated as: V (value)1 to V2 = (V2-V1) / V1 x 100. Results Improvements in the achievement of HEMI and HEMR were observed from W12 to W28 in both the colon and rectum, with more pronounced improvements in the rectum. Specifically, the proportion of patients achieving HEMI in the colon increased by 43.5% from W12 to W28 (26.7% to 38.4%), while achievement of HEMR in the colon increased by 40.0% (23.3% to 32.6%). In the rectum, the proportion of patients achieving HEMI increased by 56.4% (22.7% to 35.5%), and HEMR increased by 66.7% (17.4% to 29.1%). Additionally, the proportion of patients achieving histologic improvement and histologic remission was numerically higher at W28 compared to W12 for both the colon and rectum. Conclusion This is the first study evaluating patients with baseline BU with standardized histology assessment from both the rectum and the colon. The proportions of patients achieving histologic and histologic-endoscopic endpoints increased from W12 to W28, with a more notable improvement in the rectum. The results support the continued and increasing efficacy of MIRI in reducing and resolving inflammation in UC. Conflict of interest: Danese, Silvio: Personal Fees: AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, Vifor Lecture fees from Abbvie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer, Takeda Magro, Fernando: Fernando Magro served as speaker and received honoraria from Abbvie, Arena, Biogen, Bristol-Myers Squibb, Falk, Ferring, Hospira, Janssen, Laboratórios Vitoria, Pfizer, Lilly, Merck Sharp & Dohme, Sandoz, Takeda, UCB, Vifor. Ponich, Terry: TP has served as a consultant for Bristol Myers Squibb, Celltrion, Eli Lilly and Pfizer recently. He currently serves as an investigator on clinical research studies for Abivax, Alimentiv, AnaptysBio, Eli Lilly, Merck, Morphic Therapeutic, Pfizer/Kanyos Bio, Spyre Therapeutics and Takeda. Walsh, Alissa: Grant: Alfasigma, Helmsley Trust, Johnson & Johnson, Pfizer, Takeda Personal Fees: AbbVie, Alfasigma, Bristol Meyers Squibb, Dr Falk, Ferring, Johnson & Johnson, Lilly, Pfizer, Takeda, Tillotts Dignass, Axel: Personal Fees: AbbVie, Alfasigma, CED Service GmbH, Celltrion, Dr. Falk Pharma, Falk Foundation, Ferring, Fresenius Kabi, Gilead, High5MD, J & J, Lilly, Materia Prima, MSD, Pfizer, Pharmacosmos, Sandoz, Stada, Streamed-Up, Takeda, Tillotts, Vifor Pharma Grant Abbvie, J & J, Takeda Non-financial support Abbvie, J & J, Takeda Other: Abivax, AbbVie, Alfasigma, Dr Falk Pharma, Fewrring, J & J, Pfizer Laharie, David: Personal Fees: Board, consulting and lecture fees from Abbvie, Alfasigma, Amgen, Biocon, Celltrion, Ferring, Fresenius-Kabi, Johnson & Johnson, Lilly, MSD, Pfizer, Sandoz and Takeda Limdi, Jimmy: Speaker and Consultancy fees: Abbvie, Arena, AlfaSigma, BioHit, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Galapagos, Johnson & Johnson, MSD, Pfizer, Tillotts Kempinski, Radoslaw: Lecture fees from AbbVie, Aboca S.p.A. Societa Agricola, Ferring, Eli Lilly and company grant/research support from Takeda, Johnson & Johnson Innovative Medicine. Lewis, James: Dr. Lewis consulted or served on an advisory board or data monitoring committee for Amgen, Crohn’s & Colitis Foundation, Eli Lilly and Company, Galapagos, Janssen Pharmaceuticals (Johnson & Johnson), Merck, Odyssey Therapeutics, Pfizer, Protagonist Therapeutics, Sanofi, and Spyre Pharmaceuticals. He has had research funding or in kind support from Nestle Health Science, Takeda, Janssen Pharmaceuticals, AbbVie and Eli Lilly. He has had educational grants from Janssen. He has performed legal work on behalf of manufacturers of generic ranitidine and 3M. He owns stock in Dark Canyon Labs. Younes, Ziad: -Research grants: Abivax, AbbVie, Agomab, Genentech, Eli Lilly, Johnson and Jonhson, Mirador, Takeda -Consulting: AbbVie, BMS, Eli Lilly -Speaking honoraria: AbbVie, BMS, Eli Lilly, Johnson and Johnson, Pfizer Cohen, Erica: advisory board and consultant for Pfizer, Takeda, and PRIME Education speaker for AbbVie, Eli Lilly and Company, Janssen, and Takeda. Eastman, William: Employee and shareholder of Eli Lilly and Company. Fisher, Deborah: Employee and shareholder of Eli Lilly and Company. Tian, Tian: Employee and shareholder of Eli Lilly and Company. Rubin, David T.: Grant support: Takeda Pharmaceuticals Consultant: Abbvie, Abivax SA, Altrubio, Athos Therapeutics, Inc, Bristol-Myers Squibb, Celltrion, Connect BioPharma, Eli Lilly & Co., Genentech (Roche) Inc., Iterative Health, Janssen Pharmaceuticals, Johnson & Johnson, Merck & Co., Mirador, Odyssey Therapeutics, Pfizer, Sanofi, Spyre, Takeda Pharmaceuticals, Vedanta Biosciences, and Ventyx. Dubinsky, Marla C: Personal Fees: Consultant or Advisory Board: Abbvie, Abivax, Astra Zeneca, BMS, Celltrion, Gilead, Genentech, Janssen, Johnson and Johnson, Lilly, Merck, Pfizer, Prometheus Biosciences, Sanofi, Spyre, Target RWE, Takeda Other: Shareholder, Co-founder, Board of Directors of Trellus Health Co-Founder Mi Test Health