P0564 Optimizing Ulcerative Colitis maintenance treatment: Indirect comparison on number needed to treat among interleukin-23p19 inhibitors highlights mirikizumab’s efficacy

Abstract Background We indirectly compared the interleukin-23p19 inhibitors (IL-23p19i) mirikizumab (MIRI), risankizumab (RIS), and guselkumab (GUS) in adults with ulcerative colitis (UC) by estimating the number of patients needed to treat (NNT),1 versus placebo (PBO), for 1 additional patient to benefit after approximately (approx.) 1 year of maintenance treatment. Methods In each phase 3 trial (MIRI: NCT03518086/NCT035240922; RIS: NCT03398148/NCT033981353; GUS: NCT040334454), adults with UC received IL-23p19i or PBO intravenously for 12 weeks. Those who achieved a clinical response (CRes) on IL-23p19i after the 12-week induction were rerandomized to receive IL-23p19i (MIRI 200mg every 4 weeks Q4W; RIS 180 or 360mg every 8 weeks Q8W; GUS 100mg Q8W or 200mg Q4W]) or PBO subcutaneously.2-4 Efficacy endpoints included CRes, clinical remission (CRem), endoscopic improvement (EI), and histo-endoscopic mucosal improvement (HEMI). We estimated NNTs1 for all 3 drugs compared with PBO after approx. 1 year of maintenance, based on published (unadjusted) response rates from those phase 3 trials.3,4 We also estimated NNTs1 for MIRI based on adjusted response rates from anchored matching-adjusted indirect comparison (MAIC) with RIS and GUS at study and arm level. Patients were matched for age, sex, UC duration, UC location, modified Mayo Score, concomitant corticosteroid and/or immunosuppressant use, and inadequate response/intolerance to prior advanced UC treatment. Results NNTs for MIRI 200mg, based on adjusted rates from MAIC per treatment arm (2.8 for CRes, 3.2 for CRem, 2.9 for EI, and 3.6 for HEMI), were lower than NNTs for RIS 180mg (6.1 for CRes, 6.6 for CRem, and 5.2 for EI and HEMI). NNTs for MIRI 200mg, based on adjusted rates from MAIC per treatment arm, were also lower than NNTs for RIS 360mg (Fig 1). NNTs for MIRI 200mg, based on adjusted rates from MAIC per treatment arm (3.1 for CRes, 4.0 for CRem, 3.3 for EI, and 3.8 for HEMI), were comparable to NNTs for GUS 100mg (2.9 for CRes, 3.8 for CRem, 3.3 for EI, and 3.7 for HEMI). NNTs were also comparable for MIRI 200mg and GUS 200mg (Fig 2). MIRI NNTs were similar for each efficacy endpoint whether calculated from unadjusted or matching-adjusted response rates at the study or arm level. Conclusion MIRI achieved consistently lower NNTs than RIS across all disease-control endpoints, suggesting clinicians may need to treat approx. half as many patients with MIRI as with RIS for 1 year for 1 additional patient to benefit over PBO. NNTs for MIRI and GUS were similar, suggesting comparable efficacy. Though further studies are needed to confirm these findings, they provide valuable evidence to support the efficacy of MIRI across clinical endpoints for UC and to inform IL-23p19i selection in practice. References: 1. Laupacis A, Sackett DL, Roberts RS. N Engl J Med. 1988;318(26):1728-1733. 2. D’Haens G, et al. N Engl J Med. 2023;388(26):2444-2455. 3. Louis E, et al. JAMA. 2024;332(11):881-897. 4. Rubin DT, et al. Lancet. 2025;405(10472):33-49. Conflict of interest: Peyrin-Biroulet, Laurent: CONSULTING Abbvie, Abivax, Adacyte, Alimentiv, Alfasigma, Amgen, Apini, Banook, BMS, Celltrion, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Iterative Health, Janssen, Lilly, LifeMine, Medac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeuthics, Par’ Immune, Pfizer, Prometheus, Roche, Roivant, Samsung, Sandoz, Sanofi, Sorriso, Spyre, Takeda, Teva, ThirtyfiveBio, Tillots, Vectivbio, Vedanta, Ventyx. LECTURE Abbvie, Alfasigma, Amgen, Biogen, Celltrion, Ferring, Galapagos, Genentech, Gilead, Iterative Health, Janssen, Lilly, Medac, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, Tillots 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 Hoque, Syed Samiul: Speaker fees from Eli Lilly, BMS, and Tillotts. 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. Kwapisz, Lukasz: Speaker and Advisor for Abbvie, Johnson and Johnson, Bristol Myers Squibb, Eli Lilly and Company, Ferring, and Pfizer. Advisor for Genentech. Redondo, Isabel Maria: employee and share holder Eli Lilly Mendiolaza, Michelle: Employee and shareholder of Eli Lilly and Company. Duan, Yajie: Employee and shareholder of Eli Lilly and Company Zhu, Baojin: Employee and shareholder of Eli Lilly and Company. Maier, Sebastian: Employee and shareholder of Eli Lilly and Company Regueiro, Miguel: Advisory Boards and Consultant (both) for Abbvie, Johnson and Johnson, UCB, Takeda, Pfizer, BMS, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, Boehringer Ingelheim Pharmaceuticals Inc. (BIPI), Celltrion, Roche, Merck, Sanofi, Biocon, Abavax