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

ABSTRACT

Introduction: 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
• inflammatory bowel disease
• interleukin 12
• interleukin 17
• interleukin 23
• IL-12
• IL-17
• IL-23
• monoclonal antibody
• ustekinumab

Article highlights

• The IL-23/IL-17 axis has a pivotal role in the complex pathogenesis of inflammatory bowel diseases, which lead to the development of several therapeutics targeting different components within this pathway.

• Targeting IL-12/IL-23p40, as well as IL-23p19, seems efficacious and safe in the treatment of moderate-to-severe Crohn’s disease in recent trials. Efficacy and safety profiles in ulcerative colitis are soon expected.

• Although efficacious in other immune-mediated inflammatory diseases, blocking IL-17 or IL-17R worsens moderate-to-severe Crohn’s disease.

• The place of this novel drugs in the current treatment algorithms is under exploration.

This box summarizes key points contained in the article.

Declaration of interest

G van Assche has received financial support for research from Abbott Laboratories and Ferring Pharmaceuticals. They have also received lecture fees from Janssen Pharmaceuticals, Merck Sharp and Dohme and Abbott Laboratories. They have also received consultancy fees from PDL BioPharma, UCB Pharma, Sanofi-Aventis, Abbott Laboratories, AbbVie, Ferring Pharmaceuticals, Novartis, Biogen Idec, Janssen Biologicals, NovoNordisk, Zealand Pharma A/S, Millenium/Takeda, Shire, Novartis and Bristol-Myers Squibb. S Vermeire has received research support from Merck Sharp and Dohme, AbbVie, and UCB Pharma. They have also received lecture fees from Abbott Laboratories, AbbVie, Merck Sharp and Dohme, Ferring Pharmaceuticals and UCB Pharma and consultancy fees from Pfizer Inc, Ferring Pharmaceuticals, Shire Pharmaceuticals Group, Merck Sharp and Dohme and AstraZeneca. Finally, M Ferrante has received research support from Takeda as well as lecture fees from Ferring Pharmaceuticals, Boehringer Ingelheim, Chiesi Pharmaceuticals, Merck Sharp andn Dohme, Tillotts, Janssen Biologics, AbbVie, Takeda, Mitsubishi Tanabe, and Zeria. They’ve also received consultancy fees from AbbVie, Boehringer Ingelheim, Ferring Pharmaceuticals, Merck Sharp and Dohme and Janssen Biologics. … The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

B Verstockt is a doctoral fellow and G Van Assche, S Vermeire and M Ferrante are Senior Clinical Investigators of the Research Foundation Flanders (FWO), Belgium. B Verstockt has also received research grants by the Belgium Week of Gastroenterology and by Belgian IBD Research and Development (BIRD).