IL12/23 or selective IL23 inhibition for the management of moderate-to-severe Crohn's disease?

Abstract

The interleukin (IL)-12 family of cytokines, including IL12 and IL 23, play an important role in driving aberrant Th1 and Th17 immune responses in patients with Crohn's disease (CD). Targeting this pathway has opened new avenues for therapeutic intervention. The approval of ustekinumab, a monoclonal antibody blocking the common p40 subunit of IL12 and IL23, marked an important evolution in medical management for CD: this novel class of biologic therapy demonstrated efficacy in both patients naïve to biologics as well as in patients experiencing inadequate response or loss of response to TNF antagonists. However, as our understanding of the IL12/23 pathway has evolved, specific targeting of IL23 through its unique p19 subunit has become a focus for novel therapeutic development. IL23p19 antagonists have been shown in head-to-head trials to have superior efficacy to ustekinumab for other immune-mediated conditions such as psoriasis. In CD, phase II trials of monoclonal antibodies targeting IL23, including risankizumab and brazikumab, have shown promising results, with multiple agents now entering phase II or phase III studies. In this review, we summarize the current evidence for both anti-IL12/23p40 and anti-IL23p19 monoclonal antibodies in CD.

Keywords: Brazikumab; Crohn's disease; Guselkumab; Mirikizumab; Rizankizumab; Ustekinumab.