title: Profile of ustekinumab and its potential in patients with moderate-to-severe Crohn's disease.
abstract: The advent of anti-tumor necrosis factor (TNF)-α therapy has been a major advance in the medical management of Crohn's disease (CD). However, a significant proportion of patients with CD do not respond adequately to treatment with these agents. Primary and secondary nonresponse to anti-TNFα therapy represents a common clinical challenge, and highlights the need for the development of additional medication options for CD. The proinflammatory cytokines interleukin (IL)-12 and IL-23 are thought to play a key role in the pathogenesis of CD, and serve as a potential target for additional biologic therapies. Monoclonal antibodies targeting IL-12/23 have shown efficacy in animal models of colitis, and are currently being studied in Phase III clinical trials of CD. This review focuses on ustekinumab, a fully human immunoglobulin G1 monoclonal antibody, which blocks activity of IL-12 and IL-23 through binding the p40 subunit, and describes the current efficacy and safety data for ustekinumab in patients with CD.
authors.affiliation: Division of Gastroenterology and Hepatology, University of Virginia School of Medicine, Charlottesville, VA, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Tuskey
authors.affiliation: Division of Gastroenterology and Hepatology, University of Virginia School of Medicine, Charlottesville, VA, USA.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Behm
keywords: Crohn’s disease; clinical trials; inflammatory bowel disease; ustekinumab