Selective IL-23 Inhibition by Risankizumab Modulates the Molecular Profile in the Colon and Ileum of Patients With Active Crohn's Disease: Results From a Randomised Phase II Biopsy Sub-study

Journal of Crohn's & Colitis
Sudha VisvanathanJulián Panés

Abstract

We aimed to investigate the underlying mechanism of action of risankizumab, a monoclonal antibody targeting the IL-23 p19 subunit, previously reported to induce clinical and endoscopic remission in a randomised phase II study in patients with active Crohn's disease. Ileum and colon biopsies obtained at screening and Week 12 from a subgroup of patients [n = 106] in the risankizumab phase II study were analysed by transcriptome-wide RNA-Seq profiling. Univariate associations were assessed using linear modelling. By Week 12, risankizumab significantly decreased [p < 0.005] the expression of 1880 and 765 genes in the colon [false-discovery rate = 0.02] and ileum [false-discovery rate = 0.05], respectively. These genes were associated with the IL-23/IL-17 axis, Th1 pathway, innate immunity, and tissue turnover. Colonic transcriptomic profiles following risankizumab treatment reflected the transcriptomic changes observed in patients achieving endoscopic response and remission at Week 12 and were significantly different from placebo [p < 0.005]. The colonic transcriptomic profile, significantly modulated by risankizumab at Week 12, was indicative of suppression of pathways associated with epithelial biology. Furthermore, pathways asso...Continue Reading

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Citations

Sep 19, 2018·Expert Review of Clinical Immunology·Silvia SeddaGiovanni Monteleone
Dec 21, 2018·Expert Opinion on Biological Therapy·Fabio Salvatore MacalusoMario Cottone
Sep 17, 2020·Expert Opinion on Biological Therapy·A Al-Janabi, R B Warren
Jun 20, 2020·Crohn's & Colitis 360·Christian T WohnhaasPatrick Baum
Nov 30, 2019·Mediators of Inflammation·Fang LiuLixin Zhu
Feb 7, 2021·Journal of the European Academy of Dermatology and Venereology : JEADV·A NastC Dressler
Dec 5, 2020·ImmunoTargets and Therapy·André Jefremow, Markus F Neurath
Mar 14, 2021·Nature Reviews. Gastroenterology & Hepatology·Raja Atreya, Britta Siegmund
Apr 17, 2021·Frontiers in Immunology·Heike SchmittRaja Atreya
Jul 22, 2021·Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG·Alexander NastCorinna Dressler
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Aug 10, 2021·Expert Opinion on Investigational Drugs·Berta CaballolAzucena Salas
Aug 12, 2021·The New England Journal of Medicine·Georg SchettMarkus F Neurath
Dec 8, 2021·Best Practice & Research. Clinical Gastroenterology·André Jefremow, Markus F Neurath

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Methods Mentioned

BETA
biopsy
biopsies
ELISA
RNA-Seq

Clinical Trials Mentioned

NCT02031276

Software Mentioned

Ensembl
R
limma
STAR aligner
packages
nSolver

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