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

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.

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.

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.