Abstract Background Achieving disease clearance, which includes symptomatic, endoscopic, and histological remission, is a key step toward comprehensive disease control in the treatment of ulcerative colitis (UC). Early achievement of disease clearance by Week (W)12 of mirikizumab (miri) treatment has been associated with improved W52 clinical outcomes. This study investigates the effect of up to 4 years of miri treatment on disease clearance achievement and its sustained achievement over time in the W52 miri maintenance remitters who entered LUCENT-3 (NCT03519945), an open-label extension study. Methods Among 868 participants who received miri induction therapy in the LUCENT clinical trial program, 544 achieved clinical response at W12. Of these, 365 were rerandomized to blinded miri maintenance, and 179 achieved clinical remission at W52 and entered the open-label extension (W52 maintenance remitters). The disease clearance response rates of W52 maintenance remitters at W52 (1 year), W104 (2 years), W152 (3 years), and W212 (4 years) were analyzed. Pre-specified disease clearance (DC) was defined as symptomatic remission Mayo stool frequency (SF)=0, or SF = 1 with a ≥ 1 point decrease from baseline, and rectal bleeding (RB)=0, and histologic-endoscopic mucosal remission HEMR: histologic remission (Geboes score ≤2B.0) and endoscopic remission (Mayo endoscopy subscore (ES) of 0 or 1, excluding friability). Disease clearance was further evaluated using a more stringent definition (sDC): symptomatic remission, histologic remission, and endoscopic normalization (ES of 0). Outcomes were analyzed using modified non-responder imputation (mNRI) and observed cases (OC) to handle missing data. Results Among the W52 maintenance remitters, the proportions of patients achieving DC with continuous miri treatment at years 1, 2, 3, and 4 were 75.6%(mNRI)/75.4%(OC), 65.5%/71.1%, 63.1%/72.5%, and 50.2%/62.9%, respectively (Figure 1). The proportions of W52 maintenance remitters achieving sDC with continuous miri treatment at years 1, 2, 3, and 4 were 34.5%/33.7%, 36.9%/39.4%, 38.9%/46.6%, and 30.3%/42.3%, respectively (Figure 2). Conclusion Miri is the first anti-interleukin-23 p19 antibody to demonstrate consistent and sustained disease clearance in patients with moderately to severely active ulcerative colitis over four years of treatment. At year 4, more than 60% of W52 maintenance remitters achieved DC, and over 40% achieved the more stringent sDC (OC). Achieving sDC is an important milestone, as it is associated with a reduced risk of disease progression and is a key component of comprehensive disease control in UC. These results support the long-term efficacy and clinical relevance of miri in the management of ulcerative colitis. Conflict of interest 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. 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 Siegmund, Britta: Grant: Pfizer Other: Consultant: Abbvie, Abivax, Boehringer Ingelheim, Bristol Myers Squibb, Dr. Falk Pharma, Eli Lilly, Endpoint Health, Galapagos, Janssen/Johnson & Johnson, Materia Prima, MSD, Pfizer, Takeda, Wedbush Securities. Speaker: Abbvie, AlfaSigma, Bristol Myers Squibb, CED Service GmbH, Dr. Falk Pharma, Eli Lilly, Ferring, Galapagos, Janssen/Johnson & ampJohnson, MD Education, MSD, Pfizer, Tr1xBio. Kobayashi, Taku: Grant: AbbVie, Alfresa Pharma, Bristol Myers Squibb, Celtrion, EA Pharma, Gilead Sciences, Kyorin Pharmaceutical, Miyarisan, Mochida Pharmaceutical, Nippon Kayaku, Otsuka Holdings, Pfizer, Sekisui Medical, Takeda, Zeria Pharmaceutical Personal Fees: AbbVie, Alfresa Pharma, Alimentiv, Bristol Myers Squibb, Celltrion, Covidien, EA Pharma, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Gilead Sciences, Janssen, JIMRO, Kissei Pharmaceutical, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, MSD, Nippon Kayaku, Pfizer, Sekisui Medical, Takeda Pharmaceutical, Zeria Pharmaceutical Siegel, Corey: Consultant/Advisory Board: Abbvie, Boomerang, Celltrion, Johnson and Johnson, Lilly, Napo Pharmaceuticals, Path Healthcare, Pfizer, Prometheus Labs, Sanofi, Takeda, Trellus Health Speaker for CME activities: Abbvie, Johnson & Johnson, Pfizer, Takeda Grant support: Abbvie, Celltrion, Johnson & Johnson, Lilly, Pfizer Intellectual property: MiTest Health, LLC (software company) has a patent for a “System and Method of Communicating Predicted Medical Outcomes.” Equity Interest: Dr. Corey Siegel and Dr. Lori Siegel are co-founders of MiTest Health, LLC (software company). Technology developed by MiTest Health, LLC has been licensed to Takeda. Dr. Corey Siegel has an equity interest in Path Healthcare. Dr. Corey Siegel has an equity interest in Trellus Health Jairath, Vipul: Consulting Fees: Abbvie, Alimentiv, Amgen, Anaptys Bio, Asahi Kasei, Asieris, Astra Zeneca, Attovia, Blackbird Labs, BMS, Boehringer Ingleheim, Biomebank, Caldera, Calluna, Catalytic Health, Celltrion, Ensho, Enthera, Exeliome Biosciences, Ferring, Fresenius Kabi, Gilead, Granite Bio, GSK, Janssen, Lilly, Merck, Mountainfield, MRM Health, Nxera, Organon, OSE Immunotherapeutics, Pendopharm, Pioneering Medicine, Pfizer, Prometheus, Roche/Genentech, Sanofi, SCOPE, Shattuck Labs, Sorriso, Spyre, Synedgen, Takeda, Teva, Tillotts, Union Therapeutics, Ventus, Ventyx, Vividion, Xencor, Zealand Pharma. Pellanda, Paola: employees and shareholder of Eli Lilly and Company Keohane, Anthony: employee of HaaPACS GmbH Duan, Yajie: Employee and shareholder of Eli Lilly and Company Arora, Ravneet: Employee and shareholder of Eli Lilly and Company. Redondo, Isabel Maria: employee and share holder Eli Lilly Colombel, Jean-Frédéric: Grant: AbbVie, Janssen Pharmaceuticals, Takeda, Prometheus and Bristol Myers Squibb Lectures from: AbbVie, Roche and Takeda Other: AbbVie, Amgen, AnaptysBio, Allergan, Apini, Arena Pharmaceuticals, Astellas, Boehringer Ingelheim, Bristol Myers Squibb, candidrx Celgene, Celltrion, Clearview Curogen, Eli Lilly, Envision Pharma Ferring Pharmaceuticals, Galmed Research, Glaxo Smith Kline, Roche, Janssen Pharmaceuticals, Kaleido Biosciences, Immunic, Iterative Scopes, Landos, Microba Life Science, Merck, Mirador, Novartis, Otsuka Pharmaceutical, Owkin, Pfizer, Protagonist Therapeutics, Sanofi, Sun Pharma, Takeda, Teva, TiGenix, and is holding stock options in Intestinal Biotech Development
Magro et al. (Thu,) studied this question.