Positioning Guselkumab in The Treatment Algorithm of Patients with Crohn’s Disease

Ferdinando D’Amico,1,* Sarah Bencardino,1,* Fernando Magro,2 Axel Dignass,3 Ana Gutiérrez Casbas,4 Bram Verstockt,5 Ailsa Hart,6 Alessandro Armuzzi,7,8 Laurent Peyrin-Biroulet,9 Silvio Danese1 1Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy; 2CINTESIS@RISE, Faculty of Medicine of the University of Porto, Porto, Portugal; 3Department of Medicine I, Agaplesion Markus Hospital, Goethe University, Frankfurt/Main, Germany; 4Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, España; Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, España; 5Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, KU, Belgium; 6Inflammatory Bowel Disease Unit, St Mark’s Hospital, LNWUH NHS Trust, Harrow, UK; 7IBD Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; 8Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; 9Department of Gastroenterology, INFINY Institute, INSERM NGERE, CHRU Nancy, Vandœuvre-lès-Nancy, F-54500, France*These authors contributed equally to this workCorrespondence: Silvio Danese, Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Tel +390226432069, Fax +390282242591, Email [email protected]: Guselkumab, a selective interleukin-23 (IL-23) inhibitor, has emerged as a promising biologic therapy for the management of patients with moderate-to-severe Crohn’s disease (CD) and has been recently approved for its treatment. Unlike conventional therapies, guselkumab offers a different mechanism of action by selectively inhibiting IL-23, a key cytokine implicated in the pathogenesis of CD. IL-23 drives intestinal inflammation through activation of the Th17 cell pathway and other immune processes, positioning IL-23 inhibition as a critical therapeutic approach. In randomized Phase III clinical trials, guselkumab proved to be effective in inducing clinical and endoscopic remission both in patients naive to biologics and in patients already exposed to advanced therapies. Furthermore, no safety issues were found, supporting the well-characterized safety in other indications and its use in clinical practice also in IBD. Moreover, guselkumab has been approved for other immunomediated inflammatory disease moderate to severe plaque psoriasis, psoriatic arthritis and ulcerative colitis. This review summarizes the available evidence on efficacy and safety of guselkumab in patients with moderate to severe CD, focusing on its positioning in the treatment algorithm.Keywords: guselkumab, Crohn’s disease, IL-23, selectivity, inflammatory bowel disease