Anti-interleukin-12 and anti-interleukin-23 agents in Crohn’s disease

ABSTRACT

Introduction: Blockers of IL-12/23, as well as specific blockers of IL-23, have been investigated as options for medical therapy in inflammatory bowel disease. These biological agents include ustekinumab – the first agent of this pharmacological class which has shown clinical efficacy in psoriasis, psoriatic arthritis, and moderate-to-severe Crohn’s disease (CD) – and other monoclonal antibodies under investigation, including brazikumab, risankizumab, mirikizumab, and guselkumab.

Areas covered: This review will focus on the rationale of the blockade of IL-12/23 axis in CD, efficacy and safety data of ustekinumab derived from randomized controlled trials and real-life observational studies, and the preliminary data of the highly promising selective IL-23 inhibitors.

Expert opinion: Data from literature have demonstrated that ustekinumab holds the potential to deserve a relevant role in the management of patients with CD thanks to several properties, including the fast onset of action, the long duration of efficacy, the favorable safety profile, the systemic anti-inflammatory effect, and the peculiar way of administration. Nonetheless, additional research is warranted to determine the real value of ustekinumab, as current data are not able to answer all the questions about its effectiveness in real-life practice, and the external validity of the available results is not absolute.

KEYWORDS:

• Biologics
• brazikumab
• Crohn’s disease
• guselkumab
• mirikizumab
• risankizumab
• safety
• ustekinumab

Article highlights

• Blockers of IL-12/23, as well as specific blockers of IL-23, are novel biologics in the field of IBD.

• These biological agents include ustekinumab – already approved – and other monoclonal antibodies under investigation in IBD, including brazikumab, risankizumab, mirikizumab, and guselkumab.

• Randomized controlled trials have demonstrated that ustekinumab holds the potential to deserve a relevant role in the management of patients with Crohn’s disease.

• Preliminary data on the efficacy and safety of selective IL-23 inhibitors are highly promising.

• Head-to-head trials comparing ustekinumab with these novel IL-23 inhibitors are required.

This box summarizes key points contained in the article.

Declaration of interest

FS Macaluso served as an advisory board member for Biogen and MSD, and received lecture grants from MSD, AbbVie, and Takeda Pharmaceuticals. A Orlando served as an advisory board member for AbbVie, MSD, Takeda Pharmaceuticals, Janssen, Pfizer, and received lecture grants from AbbVie, MSD, Sofar, Chiesi, and Takeda Pharmaceuticals. 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.

Reviewer disclosures

One of the reviewers has served as a consultant for Abbvie, Allergan, Janssen and Lily, all of which have molecules in this class. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.