Expert opinion on interleukin-12/23 and interleukin-23 antagonists as potential therapeutic options for the treatment of inflammatory bowel disease

ABSTRACT

Introduction: Blockade of interleukin (IL)-12 and IL-23 is a novel therapeutic target for inflammatory bowel disease (IBD). The monoclonal antibody targeting the shared p40 subunit of IL-12 and IL23, namely ustekinumab, has been approved for Crohn’s disease (CD) and has demonstrated promising results in the treatment of ulcerative colitis. Several agents targeting the IL-23-specific p19 subunit are currently in various stages of development. These newer agents have the potential to provide safety benefits.

Areas covered: This review discusses the current state of IL-12/23 and IL-23 antagonists for the treatment of IBD. With multiple biologic classes available, we make recommendations for positioning of these agents in clinical practice.

Expert opinion: While tumor necrosis factor (TNF) antagonists remain the biologic of choice for majority of patients with moderate-to-severe IBD, IL-12/23, and IL-23 antagonists should be considered for first- or second-line therapy because of their efficacy in biologic-naïve and experienced patients. Additionally, IL-12/23 and IL-23 antagonists may be preferred over anti-TNF therapy in older patients who are at increased risk for infections and malignancy. The safety compared to anti-TNF may be even greater when one considers that concurrent immunosuppression is probably not necessary when using this class of drug, owing to the low rates of immunogenicity.

Trial registration: ClinicalTrials.gov identifier: NCT03398135.

Trial registration: ClinicalTrials.gov identifier: NCT03105128.

Trial registration: ClinicalTrials.gov identifier: NCT03616821.

Trial registration: ClinicalTrials.gov identifier: NCT02891226.

Trial registration: ClinicalTrials.gov identifier: NCT03466411.

KEYWORDS:

• Crohn’s disease
• inflammatory bowel disease
• ulcerative colitis
• ustekinumab
• interleukin-12
• interleukin-23
• interleukin-12/23
• risankizumab
• brazikumab
• mirizumab
• guselkumab

Article Highlights

• IL-12 and IL-23 are important therapeutic targets in IBD.

• IL-12/23 antagonist, ustekinumab, is effective and safe in TNF-antagonist exposed and naïve CD patients.

• There are emerging efficacy data on the use of ustekinumab in moderate to severe ulcerative colitis in TNF-antagonist exposed and naïve patients.

• Ustekinumab may have a role in chronic pouchitis and CD of the pouch. However, additional data demonstrating efficacy is necessary.

• IL-23-specific antagonists including risankizumab, brazikumab, mirikizumab, and guselkumab are in various stages of development; available efficacy and safety data are discussed.

Newer agents that target IL-23 without interference with IL-12 may provide safety benefits.

This box summarizes key points contained in the article.

Declaration of interest

RK Cross has received consulting and Advisory Board fees from Abbvie, Janssen, Takeda, and UCB and has received research funding from Abbvie. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Reviewer 1 has received speaker fees and Advisory Board fees from Abbvie, Boehringer Ingelheim, Eli Lily and Janssen and research funding from Janssen. Reviewer 2 has served as a consultant and speaker for Janssen the manufacturers of ustekinumab and guselkumab, Abbvie, the manufacturer of risankizumab and Eli Lily manufacturer of mirankizumab. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.