Biological therapy targeting the IL-23/IL-17 axis in inflammatory bowel disease

Expert Opin Biol Ther. 2017 Jan;17(1):31-47. doi: 10.1080/14712598.2017.1258399. Epub 2016 Nov 18.

Abstract

As many inflammatory bowel disease (IBD) patients do not benefit from long-term anti-tumour necrosis factor treatment, new anti-inflammatories are urgently needed. After the discovery of the interleukin (IL) 23/17 axis being pivotal in IBD pathogenesis, many different compounds were developed, targeting different components within this pathway. Areas covered: A literature search to March 2016 was performed to identify the most relevant reports on the role of the IL-23/IL-17 axis in IBD and on the different molecules targeting this pathway. First, the authors briefly summarize the immunology of the IL-23/IL-17 pathway to elucidate the mode of action of all different agents. Second, they describe all different molecules targeting this pathway. Besides discussing efficacy and safety data, they also explore immunogenicity, exposure during pregnancy and pharmacokinetics. Expert opinion: A new era in IBD treatment has recently been initiated: besides immunomodulators and TNF-antagonists, anti-adhesion molecules and monoclonal antibodies targeting the IL-23/IL-17 pathway have been developed. Biomarkers for personalized medicine are urgently needed. This therapeutic (r)evolution will further improve disease-related and patient-reported outcome, though a lot of questions should still be addressed in future years.

Keywords: Crohn’s disease; IL-12; IL-17; IL-23; inflammatory bowel disease; interleukin 12; interleukin 17; interleukin 23; monoclonal antibody; ustekinumab.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / metabolism
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Biological Therapy / methods*
  • Biological Therapy / trends
  • Cell Adhesion Molecules / antagonists & inhibitors
  • Cell Adhesion Molecules / immunology
  • Cell Adhesion Molecules / metabolism
  • Clinical Trials as Topic / methods
  • Humans
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / metabolism*
  • Interleukin-17 / antagonists & inhibitors
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism*
  • Interleukin-23 / antagonists & inhibitors
  • Interleukin-23 / immunology
  • Interleukin-23 / metabolism*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Cell Adhesion Molecules
  • Interleukin-17
  • Interleukin-23
  • Tumor Necrosis Factor-alpha