In a clinical update on inflammatory bowel disease (IBD) drugs in the developmental stage, Prof. William Sandborn (University of California San Diego, USA) said he expected a large majority of agents currently in phase 2 and phase 3 trials to reach the market. He claimed the drug armamentarium at the disposal of clinicians may double by 2025. All studies he mentioned were performed in patients with moderate-to-severe ulcerative colitis (UC) and Crohn’s disease (CD).
In IBD, 2 integrin-targeting therapies are already available: natalizumab and vedolizumab, the latter being gut-selective. Investigational anti-integrin therapies are etrolizumab (RG7413), ontamalimab, abrilumab, AJM 300, and PTG-100. Etrolizumab selectively binds the ÎČ7 subunit of the heterodimeric integrins α4ÎČ7 and αEÎČ7. Positive results in a phase 2 study in UC patients [1] paved the way for a series of trials: 6 for patients with UC and 2 for patients with CD. Prof. Sandborn expected to receive phase 3 results of etrolizumab in the fall of 2020. Abrilumab, targeting the integrin α4ÎČ7, also showed promising results in UC after 8 weeks induction therapy in a phase 2b study [2]. Ontamalimab targets the mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and showed promising results in UC [3].
Prof. Sandborn named 3 JAK inhibitors of which clinical data are available. TD-1473 is an orally administered topical pan-JAK inhibitor that is intestinally restricted, thus minimising systemic absorption. In an exploratory phase 1b study in UC, TD-1473 showed clinical response [4]; it is currently being tested in phase 2 and 3 trials. Two other JAK1 inhibitors, filgotinib and upadacitinib, showed encouraging results in phase 2 studies in CD [5,6].
Sphingosine-1-phosphate receptor 1 (S1P1)-modulators currently under investigation include fingolimod, ozanimod, etrasimod (APD334), and amiselimod. Ozanimod was tested in a preliminary trial in UC patients [7], but efficacy as well as safety requires further assessment in larger trials. In a phase 2 trial, etrasimod was effective in producing clinical and endoscopic improvements in UC patients [8].
Anti-IL-23 receptor monoclonal antibodies also hold promise for IBD treatment, Prof. Sandborn stated. He found phase 2 results of induction therapy with risankizumab in CD patients who had failed TNF inhibitors âthe most encouraging endoscopic data I have ever seen in this populationâ [9]. Two other promising anti-IL-23-agents, brazikumab and mirikizumab, are in development for both UC and CD.
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- Vermeire S, et al. Lancet. 2014 ;384(9940):309-18.
- Sandborn WJ, et al. Gastroenterology. 2019;156(4):946-957.e18.
- Vermeire S, et al. Lancet. 2017;390(10090):135-44.
- Sandborn WJ, et al. UEGW 2018, LB05.
- Vermeire S, et al. Lancet. 2017;389(10066):266-75.
- Sandborn WJ, et al. Gastroenterology. 2020 Feb 7. pii: S0016-5085(20)30167-0.
- Sandborn WJ, et al. N Engl J Med. 2016;374(18):1754-62.
- Sandborn WJ, et al. Gastroenterology. 2020;158(3):550â61.
- Feagan BG, et al. Lancet. 2017;389(10080):1699-1709.
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Table of Contents: ECCO 2020
Featured articles
Gut Microbiome as Treatment Target
Response to faecal microbiota transplantation in UC
Bioactives produced by gut bacteria to modulate immune response
Big Data Analysis
Multi-omics help describe CD phenotypes
The positive impact of genetic data on drug development
Experimental Therapies: Study Results
AMT-101: an oral human IL-10 fusion protein
Phase 2 results of first-in-class TL1A inhibitor
Open-label extension study of risankizumab: final results
Clinical remission after dose escalation of upadacitinib
Short- and Long-Term Treatment Results
Infliximab discontinuation increases relapse risk
Tofacitinib âreal-worldâ effectiveness in active UC
Subcutaneous ustekinumab as maintenance therapy in UC
Subcutaneous vedolizumab maintenance therapy in CD
Vedolizumab treatment persistence and safety
Specific Therapeutic Strategies
Impact of strategies on intestinal resection rate
Early ileocaecal resection in CD patients failing conventional treatment
Biologics before surgery in IBD do not elevate infection risk
Top-down infliximab superior to step-up in children with CD
High versus standard adalimumab in active UC
Head-to-Head Comparison of Treatments
Vedolizumab and anti-TNF therapies: a real-world comparison
Cancer Risk
Increased risk of small bowel cancer in IBD
Increased incidence of colorectal cancer and death in CD
Risk of rectal, anal cancer increased in perianal CD
Glyco-fingerprint as risk factor of UC-associated cancer
Miscellaneous Topics
Resolution of mucosal inflammation has dramatic effect
PICaSSO validated in real-life study
Re-inducing inflammation in organoids from UC patients
Role of immune cells in intestinal fibrosis
Association between meat consumption and IBD risk
CD exclusion diet corrects dysbiosis
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Role of immune cells in intestinal fibrosis
Association between meat consumption and IBD risk
Re-inducing inflammation in organoids from UC patients
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