P1007Evaluation of transmural healing in patients with moderately to severely active Crohn’s disease shows early efficacy of vedolizumab: VECTORS week 14 interim analysis

Abstract Background Transmural healing (TMH) may be associated with a lower risk of complications compared to clinical and endoscopic outcomes in Crohn’s Disease (CD) but is not a formal treatment target.1 VECTORS will evaluate TMH as part of an intestinal ultrasound (IUS)-based treatment target strategy in moderate to severe CD, with the aim of achieving a primary endpoint of corticosteroid (CS)-free endoscopic remission at wk 48 (NCT06257706; EudraCT: 2023-509096-16). The trial cohort to date and wk 14 interim data are described herein. Methods Enrolled participants follow a 48-wk treat-to-target algorithm featuring intravenous vedolizumab (VDZ) 300 mg and are randomised (1:1) to 2 groups: Group 1 has a treatment target of CS-free IUS response/TMH + clinical remission (CD Activity Index CDAI 150) + biomarker remission (C-reactive protein CRP 5 mg/L and faecal calprotectin FCP 250 μg/g), where IUS response is defined as a 25% decrease from baseline in bowel wall thickness (BWT) and TMH is defined as a BWT ≤3.0 mm and colour Doppler signal=0 in all evaluable segments; Group 2 targets CS-free clinical + biomarker remission. After VDZ induction therapy at wk 0, 2, 6, and 10, and maintenance therapy initiation at wk 14, each target assessment (wk 22, 30, 38) where the assigned target is not achieved will prompt treatment escalation using VDZ, CS, or a switch to another approved therapy. Results As of 15SEP2025, 54 of a planned 304 participants were randomised and treated with VDZ (mean age 38 y; 70% male), and 76% (41/54) had reached wk 14; 8 of the 10 early trial discontinuations occurred at 2 sites. At baseline (BL) (Table), most participants had ileal only/ileocolonic CD (82%) and were advanced therapy naive (74%); CD duration was ≤2 years in 44%, and 20% were receiving concomitant CS. Mean BL Simple Endoscopic Score for CD was 10.9. In Group 1, mean (SD) International Bowel Ultrasound Segmental Activity Score improved by 42% from 57.1 (24.1) at BL to 29.9 (23.3) at wk 14 in the terminal ileum (TI); mean (SD) BWT decreased from 5.1 (1.5) to 3.3 (1.3) mm in the TI and from 3.5 (1.5) to 2.5 (1.3) mm in the worst affected colonic segment (Figure). Across the combined cohort, improvements in mean (SD) clinical measures and median (min, max) biomarkers were observed: CDAI (BL, 295 58; wk 14, 153 92); Urgency Numerical Rating Scale (6.2 2.4; 3.4 2.8); CRP (6 0, 97 mg/L; 5 1, 83 mg/L); FCP (872 81, 10581 μg/g; 466 74, 8174 µg/g). Conclusion To date, almost 20% of the planned sample size has been enrolled. Early IUS, clinical, and biomarker data suggest VDZ is associated with early efficacy. VECTORS may support a multimodal evaluation strategy for disease monitoring. Trial recruitment continues. Reference: 1. Turner D, Ricciuto A, Lewis A, et al. STRIDE-II: an update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative of the International Organization for the Study of IBD (IOIBD): determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology. 2021;160(5):1570-1583. doi: 10.1053/j.gastro.2020.12.031 Conflict of interest: Dr. Jairath, Vipul: Vipul Jairath has received consulting/advisory board fees from AbbVie, Alimentiv Inc., Asieris, Astra Zeneca, Attovia, Biomebank, Boehringer Ingelheim, Caldera Therapeutics, Calluna, Celltrion, Domain Therapeutics, Eli Lilly, Enthera, Ensho, Exeliom Biosciences, Ferring Ventures, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Granite Bio, Janssen, Merck, Metacrine, Mountainfield, MRM Health, Nxera, Organon, OSE Immunotherapeutics, Pandion, Pendopharm, Pfizer, Prometheus Biosciences, Roche, Salvina, Sanofi, Shattuck Labs, Sorriso, Spyre, Synedgen, Takeda, Teva, Thabor Therapeutics, Union Therapeutics, Ventus, Ventyx, Vividion, Xencor, and Zealand Pharma and speaker’s fees from AbbVie, Ferring, Eli Lilly, Fresenius Kabi, Janssen, Pfizer, Takeda, and Tillotts. Vuyyuru, Sudheer K.: Sudheer K. Vuyyuru has received consulting fees from Alimentiv Inc. Ma, Christopher: Christopher Ma has received consulting fees from AbbVie, Alimentiv Inc., Amgen, Anaptys Bio, AVIR Pharma Inc, Bristol Myers Squibb, Celltrion, Domain Therapeutics, Eupraxia, Eli Lilly, Ferring, Forte Biosciences, Fresenius Kabi, Gilead, Janssen, McKesson, Mirador Therapeutics, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, Takeda, Tillotts Pharma speaker’s fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv Inc., Bristol Myers Squibb, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Merck, Organon, Pendopharm, Pfizer, Sanofi, Takeda, and Tillotts Pharma royalties from Springer Publishing and research support from AbbVie, Eli Lilly, Ferring, and Pfizer. Zou, Guangyong: Guangyong Zou has received consulting fees from Alimentiv Inc. Neustifter, Blue: Blue Neustifter is an employee of Alimentiv Inc. Agboton, Christian: Christian Agboton is an employee of and holds stock/options in Takeda Development Center Americas, Inc. Romo Bautista, Itzel: Dr. Itzel Romo Bautista is an employee of and holds stock/options in Takeda Development Center Americas, Inc. Wu, Jingang Jackie: Jingang Jackie Wu is an employee of Takeda Pharmaceuticals. Jiang, Hongyu Jeanne: Other: I am an employee of Takeda Pharmaceuticals USA, Inc. and receive stock/stock options from Takeda Pharmaceutical Company, Ltd. Allocca, Mariangela: Mariangela Allocca received consulting fees from Nikkiso Europe, Mundipharma, Janssen, AbbVie, Ferring, Galapagos, Alfasigma, Lilly, Sandoz, and Pfizer. An, Yoon-Kyo: Yoon-Kyo An has received consulting and speaker fees from AbbVie, Alimentiv Inc., Bristol Myers Squibb, Eli Lilly, Dr Falk, Ferring, Glaxo-Smith Kline, Johnson & Johnson, Pfizer, Samsung, Sandoz, Shire, Takeda Pharmaceuticals and United Clinical advisory board fees from AbbVie, Bristol Myers Squibb, Chiesi, Johnson & Johnson, Microba, NPS Medicine Wise, the Council of Therapeutic Advisory Group (CATAG), Takeda Pharmaceuticals and Xencor and research and educational support from AbbVie, Bristol Myers Squibb, Cannon, Celltrion, CR Kennedy, Chiesi, Dr Falk, Ferring, GE Healthcare, Johnson & Johnson, Pfizer, Samsung, Sandoz, Siemen, and Takeda Pharmaceuticals. Begun, Jakob: Jakob Begun has received grant/research support/speaker honoraria/advisory board fees from AbbVie, Janssen, Takeda, Pfizer, Ferring, Bristol Myers Squibb, Gilead, Tillott’s, Sandoz, Celltrion, Chiesi, Dr Falk, Microba, Glaxo Smith Klein, Merck Sharp & Dohme, Roche, Sandoz, Antara, Spyre, Xencor, Therapeutic Guidelines, Research Review, NHMRC, US Department of Defence, The Gutsy Foundation, The Gastroenterological Society of Australia, The University of Queensland, The Viertel Foundation, and The Mater Foundation and is a shareholder in Microba. Bryant, Robert V.: Robert Bryant has received grant/research support/speaker honoraria/advisory board fees from AbbVie, Ferring, Janssen, Shire, Takeda, GlaxoSmithKline, Bristol Myers Squibb, and Emerge Health and is a shareholder in Biomebank. Danese, Silvio: Silvio Danese reports consultancy fees from AbbVie, Alimentiv Inc., 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 and lecture fees from AbbVie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer, and Takeda. Dubinsky, Marla C: Marla Dubinsky has received consulting/advisory board fees from AbbVie, Abivax, Astra Zeneca, Arena Pharmaceuticals, Bristol Myers Squibb, Celltrion, Eli Lilly, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Johnson and Johnson, Merck, Pfizer, Prometheus Biosciences, Prometheus Labs, Roche, Sanofi, Spyre, and Takeda. Freire, Marcelo: I am an employee with Takeda and hold shares of the company. Novak, Kerri L.: Kerri L. Novak has received grant/research support/ speaker honoraria/ advisory board fees from AbbVie, Agmen, Bristol-Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresnius Kabi, Janssen, Pendopharm, Pfizer, and Takeda. Panaccione, Remo: Remo Panaccione has received grant/research support/speaker honoraria/advisory board fees from Abbott, AbbVie, Abbivax, Alimentiv Inc., Amgen, AnaptysBio, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galap