STELARA® targets an inflammatory gateway of Crohn's disease1-7
By targeting the upstream* regulatory cytokines IL-12 and IL-23, STELARA® may be able to disrupt the resulting inflammatory cascade.
The clinical significance of these characteristics is not fully known.
*Ustekinumab is a human IgG1k monoclonal antibody that binds with specificity to the p40 protein subunit used by both the IL-12 and IL-23 cytokines. IL-12 and IL-23 are naturally occurring cytokines that are involved in inflammatory and immune responses, such as natural killer cell activation and CD4+ T-cell differentiation and activation. In in vitro models, ustekinumab was shown to disrupt IL-12 and IL-23 mediated signaling and cytokine cascades by disrupting the interaction of these cytokines with a shared cell-surface receptor chain, IL-12Rß1. The cytokines IL-12 and IL-23 have been implicated as important contributors to the chronic inflammation that is a hallmark of Crohn’s disease.
References: 1. STELARA [package insert]. Horsham, PA: Janssen Biotech, Inc; 2016. 2. Neurath MF. IL-23: a master regulator in Crohn disease. Nat Med. 2007;13(1):26-28. 3. McKenzie BS, Kastelein RA, Cua DJ. Understanding the IL-23–IL-17 immune pathway. Trends Immunol. 2006;27(1):17-23. 4. Strober W, Zhang F, Kitani A, Fuss I, Fichtner-Feigl S. Proinflammatory cytokines underlying the inflammation of Crohn’s disease. Curr Opin Gastroenterol. 2010;26(4):310-317. 5. Fina D, Caruso R, Pallone F, Monteleone G. Interleukin-21 (IL-21) controls inflammatory pathways in the gut. Endocr Metab Immune Disord Drug Targets. 2007;7(4):288-291. 6. Geremia A, Biancheri P, Allan P, Corazza GR, Di Sabatino A. Innate and adaptive immunity in inflammatory bowel disease. Autoimmun Rev. 2014;13(1):3-10. 7. Steel AW, Mela CM, Lindsay JO, Gazzard BG, Goodier MR. Increased proportion of CD16+ NK cells in the colonic lamina propria of inflammatory bowel disease patients, but not after azathioprine treatment. Aliment Pharmacol Ther. 2011;33(1):115-126.