P1108Upadacitinib improves histologic and endoscopic-histologic outcomes in the colon and ileum of patients with moderately to severely active Crohn’s disease

Abstract Background In addition to endoscopic evaluation, histologic assessment of mucosal healing in patients with Crohn’s disease (CD) may provide further insights into the inflammatory status of their disease. Upadacitinib (UPA) is an oral Janus kinase inhibitor approved for the treatment of moderately to severely active CD that has demonstrated significantly higher rates of endoscopic remission compared with placebo (PBO) in phase 3 induction and maintenance trials.1 This post hoc analysis evaluated histologic outcomes in patients with CD treated with UPA vs PBO from the phase 3 trials. Methods Clinical responders to 12 wks induction of UPA 45 mg (UPA45) once daily (QD; U-EXCEL, U-EXCEED) were rerandomised to UPA 15 mg (UPA15) QD, UPA 30 mg (UPA30) QD, or PBO for 52 wks during maintenance (U-ENDURE). Biopsy collection was optional, including 2 specimens from each of 5 intestinal segments obtained from the edge of ulcers or most inflamed mucosa during endoscopy at screening, wk 12 (induction), and wk 52 (maintenance). The worst biopsy fragment of each segment was scored by central readers, with the highest score for a given feature across segments. The proportion of patients achieving histologic remission by Colonic/Ileal Global Histology Activity Score (CGHAS/IGHAS score ≤2), histologic remission alternatively defined as complete absence of mucosal neutrophils in epithelium and lamina propria and no epithelial damage, erosions and ulcers, and endoscopic-histologic remission defined as achieving both endoscopic remission (SES-CD Total Score ≤4 and ≥2-point reduction versus baseline and no subscore 1 in any individual variable) and histologic remission per alternative definition was assessed at wks 12 and 52 among patients with abnormal histology at baseline. Adjusted treatment differences between UPA and PBO were assessed using the Cochran-Mantel-Haenszel test. Safety was not assessed in this analysis but was published previously.1 Results 122 (PBO) and 247 (UPA) patients had histology data available at baseline, of which 115 (PBO) and 231 (UPA) had abnormal histology. A greater proportion (%) of patients receiving UPA vs PBO achieved: histologic remission by CGHAS (wk12: PBO 8.4, UPA45 21.6; wk52: PBO 6.2, UPA15 19.6, UPA30 25.0) and IGHAS (wk12: PBO 10.8, UPA45 18.3; wk52: PBO 0.3, UPA15 9.9, UPA30 11.9; Fig 1), histologic remission by alternative definition (wk12: PBO 9.6, UPA45 21.0; wk52: PBO 1.3, UPA15 15.6, UPA30 16.9; Fig 2A), and endoscopic-histologic remission (wk12: PBO 2.6, UPA45 10.4; wk52: PBO 0, UPA15 13.8, UPA30 15.4; Fig 2B). Conclusion In patients with moderately to severely active CD, UPA demonstrated improved histologic and endoscopic-histologic remission rates at induction (wk 12) and maintenance (wk 52) compared to PBO. Reference: 1. Loftus, E.V. et al.N Engl J Med. Upadacitinib induction and maintenance therapy for Crohn’s disease. 2023; 388;1966-1980 Conflict of interest: Prof. Dr. Magro, Fernando: Has been a speaker and has received honoraria for services from AbbVie, Biogen, Falk, Ferring, Hospira, Laboratorios Vitoria, Merck, and Vifor. Jairath, Vipul: Received consulting/advisory board fees from AbbVie, Alimentiv, Arena, Asahi Kasei Pharma, Asieris, Astra Zeneca, Avoro Capital, Bristol Myers Squibb, Celltrion, Eli Lilly, Endpoint Health, Enthera, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GlaxoSmithKline, Genentech, Gilead, Innomar, JAMP, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus Biosciences, Reistone Biopharma, Roche, Roivant, Sandoz, Scope Eyecare, Second Genome, Sorriso, Takeda, TD Securities, Teva, TopiVert, Ventyx, Vividion received speaker’s fees from AbbVie, Ferring, Bristol Myers Squibb, Galapagos, Janssen, Pfizer, Takeda, and Fresenius Kabi. Peyrin-Biroulet, Laurent: Received consulting fees from AbbVie, Abivax, Adacyte, Alimentiv, Alfasigma, Amgen, Apini, Applied Molecular Transport, Arena, Banook, BMS, Celltrion, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, GSK, IAG Image Analysis, Index, Inotrem, Iterative Health, Janssen, Lilly, LifeMine, Medac, Mopac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeutics, Par’ Immune, Pfizer, Prometheus, Roche, Roivant, Samsung, Sandoz, Sanofi, Sorriso, Spyre, Takeda, Teva, ThirtyfiveBio, Tillots, Vectivbio, Vedanta, and Ventyx. He has received lecture fees from AbbVie, Amgen, Arena, Biogen, Celltrion, Ferring, Galapagos, Genentech, Gilead, Iterative Health, Janssen, Lilly, Medac, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, and Tillots. van Haaren, Stijn: Employee of AbbVie and may own stock options Dubcenco, Elena: Employee of AbbVie and may own stock options Ogholikhan, Sina: Employee of AbbVie and may own stock options. Garrison, Andrew: Employee/contractor of AbbVie and may own AbbVie stock or options. Abraham, Bincy: Consultant for Abbvie, Johnson and Johnson, Pfizer, Takeda, Celltrion, Lilly, Sanofi and on the Speaker’s Bureau for Abbvie, Johnson and Johnson, Pfizer, Takeda, Lilly.