Novel oral targeted therapies in inflammatory bowel disease

White, Jonathan Richard and Philips, Frank and Monaghan, Tanya M. and Fateen, Waleed and Samuel, Sunil and Ghosh, Subrata and Moran, Gordon W. (2018) Novel oral targeted therapies in inflammatory bowel disease. Alimentary Pharmacology & Therapeutics, 47 (12). pp. 1610-1622. ISSN 1365-2036

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Abstract

Background: There is a great unmet clinical need for efficacious, tolerable, economical and orally administrated drugs for the treatment of inflammatory bowel disease (IBD). New therapeutic avenues have become possible including the development of medications that target specific genetic pathways found to be relevant in other immune mediated diseases.

Aims: To provide an overview of recent clinical trials for new generation oral targeted medications that may have a future role in IBD management.

Methods: Pubmed and Medline searches were performed up to 01/03/18 using keywords: ‘IBD’, ‘UC’, ‘CD’, ‘inflammatory bowel disease’ ‘ulcerative colitis’, Crohn’s disease’ in combination with ‘phase’, ‘study’, ‘trial’, and ‘oral’. A manual search of the clinical trial register, article reference lists, abstracts from meetings of Digestive Disease Week, United European Gastroenterology Week and ECCO congress were also conducted.

Results: In randomised controlled trials primary efficacy endpoints were met for tofacitinib (JAK 1/3 inhibitor-phase III), upadacitinib (JAK 1 inhibitor-phase II) and AJM-300 (α4-integrin antagonist-phase II) in ulcerative colitis. Ozanimod (S1P receptor agonist-phase II) also demonstrated clinical remission. For Crohn’s disease, filgotinib (JAK1 inhibitor-phase II) met primary endpoints and laquinimod (quinolone-3-carboxide small molecule-phase II) was also efficacious. Trials using mongersen (SMAD7 inhibitor) and vidofludimus (dihydroorotate dehydrogenase inhibitor) have been halted.

Conclusions: This is potentially the start of an exciting new era in which multiple therapeutic options are at the disposal of physicians to treat IBD on an individualised basis. Head-to-head studies with existing treatments and longer term safety data are needed for this to be possible.

Item Type: Article
Additional Information: This is the peer reviewed version of the following article: White JR, Phillips F, Monaghan T, et al. Novel oral‐targeted therapies in inflammatory bowel disease. Aliment Pharmacol Ther. 2018;00:1–13. https://doi.org/10.1111/apt.14669 which has been published in final form at https://onlinelibrary.wiley.com/doi/abs/10.1111/apt.14669 This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Keywords: Inflammatory bowel disease, Crohn’s disease, ulcerative colitis, immunotherapy
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Nottingham Digestive Diseases Centre
University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine
Identification Number: https://doi.org/10.1111/apt.14669
Depositing User: Jones, Natalie
Date Deposited: 26 Mar 2018 08:24
Last Modified: 27 Jul 2018 09:30
URI: http://eprints.nottingham.ac.uk/id/eprint/50666

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