Clinical utility of ustekinumab in Crohn’s disease
Paulo Gustavo Kotze,1,2 Christopher Ma,1 Abdulelah Almutairdi,1,3 Remo Panaccione1 1Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; 2Inflammatory Bowel Disease Outpatient Clinics, Colorectal Surgery...
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Dove Medical Press
2018
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oai:doaj.org-article:25cb5d38074445dd8d6d6de00648566b2021-12-02T06:18:57ZClinical utility of ustekinumab in Crohn’s disease1178-7031https://doaj.org/article/25cb5d38074445dd8d6d6de00648566b2018-02-01T00:00:00Zhttps://www.dovepress.com/clinical-utility-of-ustekinumab-in-crohns-disease-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Paulo Gustavo Kotze,1,2 Christopher Ma,1 Abdulelah Almutairdi,1,3 Remo Panaccione1 1Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; 2Inflammatory Bowel Disease Outpatient Clinics, Colorectal Surgery Unit, Catholic University of Paraná, Curitiba, Brazil; 3Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia Abstract: 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. Keywords: ustekinumab, Crohn’s disease, interleukinKotze PGMa CAlmutairdi APanaccione RDove Medical PressarticleustekinumabCrohn’s diseaseinterleukin.PathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 11, Pp 35-47 (2018) |
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DOAJ |
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EN |
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ustekinumab Crohn’s disease interleukin. Pathology RB1-214 Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
ustekinumab Crohn’s disease interleukin. Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Kotze PG Ma C Almutairdi A Panaccione R Clinical utility of ustekinumab in Crohn’s disease |
| description |
Paulo Gustavo Kotze,1,2 Christopher Ma,1 Abdulelah Almutairdi,1,3 Remo Panaccione1 1Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; 2Inflammatory Bowel Disease Outpatient Clinics, Colorectal Surgery Unit, Catholic University of Paraná, Curitiba, Brazil; 3Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia Abstract: 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. Keywords: ustekinumab, Crohn’s disease, interleukin |
| format |
article |
| author |
Kotze PG Ma C Almutairdi A Panaccione R |
| author_facet |
Kotze PG Ma C Almutairdi A Panaccione R |
| author_sort |
Kotze PG |
| title |
Clinical utility of ustekinumab in Crohn’s disease |
| title_short |
Clinical utility of ustekinumab in Crohn’s disease |
| title_full |
Clinical utility of ustekinumab in Crohn’s disease |
| title_fullStr |
Clinical utility of ustekinumab in Crohn’s disease |
| title_full_unstemmed |
Clinical utility of ustekinumab in Crohn’s disease |
| title_sort |
clinical utility of ustekinumab in crohn’s disease |
| publisher |
Dove Medical Press |
| publishDate |
2018 |
| url |
https://doaj.org/article/25cb5d38074445dd8d6d6de00648566b |
| work_keys_str_mv |
AT kotzepg clinicalutilityofustekinumabincrohnrsquosdisease AT mac clinicalutilityofustekinumabincrohnrsquosdisease AT almutairdia clinicalutilityofustekinumabincrohnrsquosdisease AT panaccioner clinicalutilityofustekinumabincrohnrsquosdisease |
| _version_ |
1718399980445630464 |