A safety assessment of biological therapies targeting the IL-23/IL-17 axis in inflammatory bowel diseases

ABSTRACT

Introduction: Many different compounds targeting the interleukin 23/17 axis have been developed and successfully studied in several autoimmune diseases, including inflammatory bowel diseases. Nevertheless, interfering with key immunological pathways raises potential safety concerns. This review focuses on the safety profile of these novel biological therapies.

Areas covered: A literature search until March 2017 was performed to collect safety data on different compounds targeting this pathway, with emphasis on ustekinumab and secukinumab. Firstly, the authors discuss briefly how genetics can inform about potential safety issues. Secondly, they extensively describe safety issues (common adverse events, infections, malignancies…), immunogenicity, exposure to ustekinumab in specific populations and provide advice for vaccination. Finally, they address safety profiles of secukinumab and other biological targeting the IL-23/17 axis in IBD.

Expert opinion: Current evidence suggests that ustekinumab therapy overweigh the potential drug-related risks. Additional safety data beyond randomized-controlled trials, derived from statistically powered, large prospective studies with long-term follow-up are urgently needed to assess the real-life ustekinumab-related risks and to establish the correct position of these novel class of biologicals in IBD treatment. Combining immunomodulators with ustekinumab seems to be safe, though prospective data specifically addressing this topic are currently missing. Similarly, the combination of different biological therapies still has to be studied.

KEYWORDS:

• Ustekinumab
• secukinumab
• Crohn’s disease
• psoriasis
• IBD
• autoimmunity
• infection
• malignancy
• safety
• side-effects
• mortality
• immunogenicity
• interleukin 23
• interleukin 17
• IL-23
• IL-17

Article highlights

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

• Genetics can inform us about potential safety issues.

• Targeting IL-12/IL-23p40 seems safe in the treatment of moderate-to-severe Crohn’s disease, psoriasis and psoriatic arthritis with regard to infections, malignancies, cardiovascular diseases, mortality…

• Targeting IL-17A and IL-17RA is ineffective, with a tendency to worsening of the disease, and leads to major safety issues in Crohn’s disease, whereas it is efficacious and safe in psoriasis and psoriatic arthritis.

• Additional safety data beyond randomized-controlled trials are urgently needed.

This box summarizes key points contained in the article.

Declaration of interest

B Verstockt is a doctoral fellow and S Vermeire, G Van Assche 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, the Belgian IBD Research and Development (BIRD) and the European Crohn’s and Colitis Organization (ECCO).

B Verstockt received speakers fee from Ferring Pharmaceuticals. G Van Assche received financial support for research from Abbott and Ferring Pharmaceuticals; lecture fees from Janssen, MSD and Abbott; consultancy fees from PDL BioPharma, UCB Pharma, Sanofi-Aventis, Abbott, Abbvie, Ferring, Novartis, Biogen Idec, Janssen Biologics, NovoNordisk, Zealand Pharma A/S, Millenium/Takeda, Shire, Novartis and Bristol Mayer Squibb. S Vermeire received financial support for research from MSD, Abbvie and UCB Pharma; lecture fees from Abbott, Abbvie, Merck Sharpe & Dohme, Ferring Pharmaceuticals and UCB Pharma; consultancy fees from Pfizer, Ferring Pharmaceuticals, Shire Pharmaceuticals Group, Merck Sharpe & Dohme, and AstraZeneca Pharmaceuticals. M Ferrante received financial support for research from Takeda; lecture fees from Ferring, Boehringer-Ingelheim, Chiesi, Merck Sharpe & Dohme, Tillotts, Janssen Biologics, AbbvieTakeda, Mitsubishi Tanabe, Zeria; consultancy fees from Abbvie, Boehringer-Ingelheim, Ferring, Merck Sharpe & 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 disclose

Additional information

Funding

This paper has not been funded.