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.
Keywords: Crohn’s disease; brazikumab; guselkumab; inflammatory bowel disease; interleukin-12; interleukin-12/23; interleukin-23; mirizumab; risankizumab; ulcerative colitis; ustekinumab.