System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Review Epublish

PubMed: 42739673 DOI: 10.3390/jcm15176667

Guselkumab in Inflammatory Bowel Disease: Mechanism, Clinical Efficacy, Safety, and Treatment Positioning.

J Clin Med 15(17)

Authors: Laura White, Esha Sharma, Jimmy Limdi, Shahida Din, Kamal Patel, Sailish Honap

Affiliations

  • Department of Gastroenterology, London Northwest University Healthcare Trust, London SW17 0QT, UK.
  • Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London SE1 7EH, UK.
  • Manchester Academic Health Sciences Faculty of Biology, Medicine & Health, University of Manchester, Manchester BL9 7TD, UK.
  • IBD Section, Department of Gastroenterology, Northern Care Alliance NHS Foundation Trust, Manchester M6 8HD, UK.
  • Edinburgh Inflammatory Bowel Diseases Unit, NHS Lothian, Edinburgh EH4 2XU, UK.
  • Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, UK.
  • Department of Gastroenterology, St George's University Hospital NHS Foundation Trust, London SW17 0QT, UK.
  • Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London SE1 9RT, UK.
  • Institute of Infection and Immunology, City St George's Hospital, University of London, London SW17 0RE, UK.

Abstract

Guselkumab is a monoclonal antibody directed against the p19 subunit of interleukin-23 (IL-23), thereby preventing IL-23 binding to the IL-23 receptor. IL-23 is a key driver of immune dysregulation and chronic inflammation in inflammatory bowel disease (IBD), making selective IL-23 inhibition an established therapeutic strategy in both Crohn's disease and ulcerative colitis. Guselkumab is the most recently approved IL-23p19 inhibitor for the treatment of both major forms of IBD. It is the first IL-23p19 inhibitor to offer a fully subcutaneous induction regimen, and preliminary phase III data has suggested potential benefits for patients with perianal Crohn's disease. In registrational trials, there were significant improvements across multiple clinical and endoscopic endpoints in comparison to ustekinumab, although these trials were not powered for formal superiority testing. This narrative review summarises the biological rationale for IL-23 blockade, reviews the available clinical evidence, discusses practical considerations for its use, and considers its place in the landscape of IBD treatments.

MeSH

Interleukin-23, Safety, Inflammatory Bowel Diseases, Therapeutics, Colitis, Ulcerative