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Clinical utility of ustekinumab in Crohn’s disease

The introduction of anti-tumor necrosis factor (TNF) therapy marked an important milestone in the management of moderate-to-severe Crohn’s disease (CD). However, there remains a pressing demand for alternative therapeutic options for patients with primary nonresponse, secondary loss of response, or...

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Detalles Bibliográficos
Autores principales: Kotze, Paulo Gustavo, Ma, Christopher, Almutairdi, Abdulelah, Panaccione, Remo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810512/
https://www.ncbi.nlm.nih.gov/pubmed/29445293
http://dx.doi.org/10.2147/JIR.S157358
Descripción
Sumario:The introduction of anti-tumor necrosis factor (TNF) therapy marked an important milestone in the management of moderate-to-severe Crohn’s disease (CD). However, there remains a pressing demand for alternative therapeutic options for patients with primary nonresponse, secondary loss of response, or intolerable side effects to conventional treatment and TNF antagonists. Ustekinumab (UST) is a fully human IgG1κ monoclonal antibody that inhibits the p40 subunit shared by the proinflammatory cytokines, the interleukin (IL)-12 and -23. This blockade leads to dampening of the inflammatory cascade and differentiation of inflammatory T cells. The clinical development program for UST in CD includes dose finding Phase II (Crohn’s Evaluation of Response to Ustekinumab Anti-Interleukin-12/23 for Induction [CERTIFI]) and the pivotal Phase III (UNITI) trials that demonstrated both the clinical efficacy and safety in anti-TNF-naive and anti-TNF-exposed patients. Real-world evidence has further defined the role of UST in CD management. In this review, we discuss the mechanism of action of UST, describe the results of the randomized controlled trials with this agent, and review the real-world efficacy and safety data from observational cohorts. Finally, we identify areas of future research in the IL-12/23 inflammatory pathway and discuss the positioning of this novel therapeutic option in CD treatment algorithms.