Novel oral targeted therapies in inflammatory bowel disease

White, Jonathan Richard; Philips, Frank; Monaghan, Tanya M.; Fateen, Waleed; Samuel, Sunil; Ghosh, Subrata; Moran, Gordon W.

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.

Citation

White, J. R., Philips, F., Monaghan, T. M., Fateen, W., Samuel, S., Ghosh, S., & Moran, G. W. (2018). Novel oral targeted therapies in inflammatory bowel disease. Alimentary Pharmacology and Therapeutics, 47(12), 1610-1622. https://doi.org/10.1111/apt.14669

• Journal Article Type: Article
• Acceptance Date: Mar 25, 2018
• Online Publication Date: Apr 19, 2018
• Publication Date: Jun 30, 2018
• Deposit Date: Mar 26, 2018
• Publicly Available Date: Apr 20, 2019
• Journal: Alimentary Pharmacology & Therapeutics
• Print ISSN: 0269-2813
• Electronic ISSN: 1365-2036
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 47
• Issue: 12
• Pages: 1610-1622
• DOI: https://doi.org/10.1111/apt.14669
• Keywords: Inflammatory bowel disease, Crohn’s disease, ulcerative colitis, immunotherapy
• Public URL: https://nottingham-repository.worktribe.com/output/944298
• Publisher URL: https://onlinelibrary.wiley.com/doi/abs/10.1111/apt.14669
• 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.
• Contract Date: Mar 26, 2018