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Peer-reviewedCC BY-NCEGastroenterology

Targeting the IL-23 pathway in inflammatory bowel disease: from cytokine inhibition to oral IL-23 receptor blockade.

  • Sailish Honap1,2
  • Michael Colwill1,2
  • Axel Dignass3
  • Vipul Jairath4,5
  • Fernando Magro6
  • Silvio Danese7
  • Laurent Peyrin-Biroulet8
8 affiliations
  1. 1Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK.
  2. 2Infection and Immunity Research Institute, City St George's, University of London, London, UK.
  3. 3Department of Medicine I, Agaplesion Markus Hospital, Goethe University, Frankfurt, Germany.
  4. 4Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada.
  5. 5Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.
  6. 6CINTESIS@RISE Department, Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
  7. 7Department of Gastroenterology and Digestive Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy.
  8. 8Northwestern Medicine, Digestive Health Institute, Chicago, Illinois, USA.
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Abstract

Interleukin (IL)-23 inhibition is now an established therapeutic strategy in inflammatory bowel disease (IBD), supported by the efficacy of selective IL-23p19 monoclonal antibodies in both Crohn's disease (CD) and ulcerative colitis (UC). Advances in peptide engineering have also enabled direct oral targeting of the IL-23 receptor (IL-23R), introducing an alternative approach to inhibition of the same inflammatory pathway. This narrative review examines the biological rationale for targeting the IL-23-IL-23R axis and the clinical evidence establishing selective IL-23p19 inhibition in IBD. Particular attention is given to the clinical development of icotrokinra, an oral macrocyclic peptide IL-23R antagonist. Phase 3 studies in psoriasis have established the efficacy of oral IL-23R antagonism, while the phase 2b ANTHEM-UC study has provided clinical evidence of efficacy in IBD, with improvements in clinical and endoscopic outcomes accompanied by translational evidence of pathway suppression. Ongoing phase 3 programmes in UC and CD will determine whether oral IL-23R antagonism can achieve durable clinical and endoscopic efficacy and establish its place alongside existing IL-23p19 monoclonal antibodies. If successful, this approach could represent a broader shift towards highly selective oral targeting of extracellular inflammatory pathways that have traditionally required biological therapy.

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Cite

BibTeXRIS
BibTeX
@article{honap2026targeting,
  title = {{Targeting the IL-23 pathway in inflammatory bowel disease: from cytokine inhibition to oral IL-23 receptor blockade.}},
  author = {Sailish Honap and Michael Colwill and Axel Dignass and Vipul Jairath and Fernando Magro and Silvio Danese and Laurent Peyrin-Biroulet},
  journal = {EGastroenterology},
  year = {2026},
  month = oct,
  doi = {10.1136/egastro-2026-100708},
  url = {https://europepmc.org/article/MED/42968944},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Targeting the IL-23 pathway in inflammatory bowel disease: from cytokine inhibition to oral IL-23 receptor blockade.
AU  - Sailish Honap
AU  - Michael Colwill
AU  - Axel Dignass
AU  - Vipul Jairath
AU  - Fernando Magro
AU  - Silvio Danese
AU  - Laurent Peyrin-Biroulet
PY  - 2026
DA  - 2026/10/30
JO  - EGastroenterology
DO  - 10.1136/egastro-2026-100708
UR  - https://europepmc.org/article/MED/42968944
AB  - Interleukin (IL)-23 inhibition is now an established therapeutic strategy in inflammatory bowel disease (IBD), supported by the efficacy of selective IL-23p19 monoclonal antibodies in both Crohn's disease (CD) and ulcerative colitis (UC). Advances in peptide engineering have also enabled direct oral targeting of the IL-23 receptor (IL-23R), introducing an alternative approach to inhibition of the same inflammatory pathway. This narrative review examines the biological rationale for targeting the IL-23-IL-23R axis and the clinical evidence establishing selective IL-23p19 inhibition in IBD. Particular attention is given to the clinical development of icotrokinra, an oral macrocyclic peptide IL-23R antagonist. Phase 3 studies in psoriasis have established the efficacy of oral IL-23R antagonism, while the phase 2b ANTHEM-UC study has provided clinical evidence of efficacy in IBD, with improvements in clinical and endoscopic outcomes accompanied by translational evidence of pathway suppression. Ongoing phase 3 programmes in UC and CD will determine whether oral IL-23R antagonism can achieve durable clinical and endoscopic efficacy and establish its place alongside existing IL-23p19 monoclonal antibodies. If successful, this approach could represent a broader shift towards highly selective oral targeting of extracellular inflammatory pathways that have traditionally required biological therapy.
SN  - 2766-0125
SN  - 2976-7296
ER  -