Investigational drugs in phase I and phase II clinical trials targeting interleukin 23 (IL23) for the treatment of Crohn's disease.

INTRODUCTION: Medical therapy for Crohn's disease (CD) is directed at controlling intestinal inflammation to prevent development of disease-related complications. Not all patients will respond to currently available treatments and thus, novel therapies are needed. The interleukin (IL)-23 cytokine axis is implicated in CD pathogenesis and so targeting this pathway has become an important focus for drug development.

AREAS COVERED: This review summarizes the role of the IL23 cytokine pathway in CD pathogenesis and appraises phase I and II clinical trial data for novel IL23p19 specific monoclonal antibodies for the treatment of CD. The evidence for risankizumab (BI655066/ABBV066), brazikumab (MEDI2070, formerly AMG139), guselkumab (CNTO1959), tildrakizumab (MK3222), and mirikizumab (LY3074828) is reviewed; moreover, future applications for these agents are considered.

EXPERT COMMENTARY: Targeting the specific p19 subunit of IL23 is a promising strategy in CD. Two multicenter, randomized, placebo-controlled phase II clinical trials have evaluated risankizumab and brazikumab. Both studies indicate that IL23-specific blockade is likely to be a safe and effective alternative to current biologics, including the TNF antagonists vedolizumab and ustekinumab. Confirmatory Phase 3 studies are underway. Ultimately, comparative effectiveness trials will be necessary to define the role of IL23-specific antagonists in CD treatment algorithms.