Fibrosis occurs in most Crohn’s Disease (CD) patients, although it only becomes clinically apparent in those who develop stenotic disease. Fibroblasts are considered the main cell type contributing to fibrosis by production and remodelling of the extracellular matrix. Recently, changes have been shown in the relative abundance of different fibroblast subsets in the inflamed intestine of IBD patients. However, the abundance of fibroblast subsets and their spatial localisation in fibrostenotic IBD tissue are currently unknown. The overall aim of this project is to unravel the role of fibroblast subsets in the pathogenesis of fibrostenotic CD and to identify novel therapeutic targets.
As a first objective, we will map the differences in abundance and spatial distribution of fibroblast subsets in patients with inflammatory and stenotic CD using a unique 40-marker fibroblast Imaging Mass Cytometry (IMC) antibody panel. Thereafter, as a second objective, we will investigate (pathogenic) fibroblast subsets derived from fibrostenotic lesions in CD patients using a fibroblast-rich, three-dimensional organoid-based model. Lastly, we will assess in CD patients the effects of Janus kinase (JAK) inhibition on the relative abundance of identified fibroblast subsets.
The pathogenesis and course of Inflammatory Bowel Disease (IBD) are heterogeneous and have striking age-dependent characteristics. In particular, children with very early-onset IBD (VEO-IBD) show a higher incidence of unclassified IBD and develop courses different from adult-onset forms. VEO-IBD is a rare condition, but the incidence is increasing globally at an alarming pace. Notably, VEO-IBD patients often fail to respond to conventional therapies and show life-threatening conditions.
In paradigmatic studies, we have previously reported IL-10R deficiencies as a monogenic cause in children with intractable VEO-IBD. Based on knowledge of the molecular disease mechanisms, IL-10R-deficient patients could be cured by allogeneic haematopoietic stem cell transplantation. This prime example of translational research has shifted paradigms by demonstrating the relevance of genetics for the treatment of VEO-IBD patients. Our genetic screen of one of the largest international VEO-IBD cohorts has revealed disease-causing mutations in approximately 20% of analysed patients (>60 genetic entities) and suggested optimised treatment for a significant number of children. However, most VEO IBD patients still lack definitive diagnosis and the disease mechanisms remain largely elusive.
This year, available funding for ECCO Fellowships and Grants Programme (F&G) increased to 1.9 Million Euros for this year’s Call 2023 (to be awarded ECCO’24), this is the largest funding volume to date. With diverse funding streams for innovative research and international collaborations such as the Pioneer Award and the new Global Grant as well as those specifically for early career scientists, Dieticians and Nurses, the ECCO F&G Programme has really grown in the last five years.
The return of a physical ECCO Congress finally gave me the chance to interview people in person for ECCO News. So, after an early morning start, the outgoing Chair of Y-ECCO, Charlotte Hedin, and I sat down to talk about what led her into gastroenterology, the impact of moving country mid-career and the Y-ECCO Communication Toolbox, which has recently been made available on the ECCO e-Learning Platform.
Guselkumab plus golimumab combination therapy versus guselkumab or golimumab monotherapy in patients with ulcerative colitis (VEGA): A randomised, double-blind, controlled, phase 2, proof-of-concept trial
Despite a growing armamentarium of advanced therapies for Ulcerative Colitis (UC), fewer than 40% of patients maintain clinical remission at 12 months . Combination therapy utilising dual biologic or small molecule agents can be considered in highly selected, medically refractory cases; however, robust data to support dual therapy in routine clinical practice are still lacking . Inhibitors of TNF-α and IL-23 have demonstrated efficacy in the treatment of UC [3,4]. Data emerging from animal studies have suggested that their use in combination reduces colitis synergistically and may be more efficacious than treatment with either monotherapy .
This randomised double-blinded controlled phase 2 trial, named the VEGA trial, was conducted across 54 sites internationally and aimed to determine the efficacy and safety of combination therapy with guselkumab (GUS), an IL-23 p19 antagonist, plus golimumab (GOL), a TNF-α inhibitor, compared with either monotherapy in UC.
Intestinal ultrasound (IUS) is an inexpensive, non-invasive, safe and repeatable, dynamic cross-sectional imaging technique for IBD. It has been demonstrated to be accurate and reliable both for initial diagnosis of IBD and for follow-up monitoring . Huge advantages of IUS are that it does not need any prior preparation of the patient and provides a real-time result. IUS can be performed in various hospital settings, which makes it the only point-of-care (POC) imaging technique available today .
The impact of POC IUS on daily decision making and the evolution in its use over the years were evaluated in this retrospective study, which included two consecutive cohorts of IBD patients in a real-world outpatient setting. The first cohort of patients, included between January 2016 and July 2018, was compared with a second cohort collected between October 2019 and December 2019.
Therapeutic strategies for Crohn’s Disease have evolved over the past decade, with mounting evidence that achieving deep remission (defined as clinical, biochemical and endoscopic remission) is associated with better long-term outcomes [1, 2]. Combination therapy with infliximab and azathioprine has been shown to be superior to either infliximab or azathioprine monotherapy in achieving clinical remission and endoscopic healing in azathioprine-naive patients, thus supporting the paradigm of early disease management and the use of treatment combinations to increase treatment success . Concerns regarding the implications of long-term combination therapy, such as infections and lymphoproliferative disorders, have provided the rationale for a formal clinical trial of treatment de-escalation.
The aim of this trial was to compare the relapse rate and the time spent in remission over 2 years between patients continuing combination therapy and those stopping infliximab or immunosuppressant therapy.
After two consecutive virtual events, the Y-ECCO Basic Science Workshop was back with a face-to-face meeting, reaching its 9th edition on March 1, 2023, in Copenhagen.
This Workshop aims to involve young fellows in a fully comprehensive manner, giving them the opportunity to present relevant data that were submitted for the scientific programme and discuss their views with successful key opinion leaders in the field of Inflammatory Bowel Diseases (IBD), with special focus on basic and translational research. All sessions open with a hot topic presented by an invited senior specialist, followed by excellent presentations by selected young researchers. The secret of the constant success of this initiative is the friendly atmosphere, which allows participating Y-ECCO Members to increase their knowledge while also preparing for more challenging stages.
I do hope you all enjoyed the ECCO Congress in Copenhagen and made the most of the opportunity to “get physical” again for the first time in too long! I’m sure many will agree that, although virtual conferencing has its positives, much of what makes ECCO such a special organisation to be part of can only be fully realised in person. The fact that this year’s meeting was the first in-person ECCO Congress since before the pandemic only added to the sense of excitement, and the meeting’s content did not disappoint. As is often the case, contributions from Y-ECCO Members made up a sizeable proportion of the original research presented: 58 oral presentations were selected to be presented by Y-ECCO Members and a total of ten Y-ECCO Members were awarded prizes. This again underscores the essential role played by Y-ECCO within ECCO, as a new generation of IBD experts are ushered in.
After two years of virtual meetings, the main goal of the 18th ECCO Congress, held in Copenhagen (March 1–4, 2023), was “Let’s get physical”. During this conference we enjoyed the face-to-face interaction, which provided a positive boost to the 8th H-ECCO Masterclass. The aim of our meeting was not only to discuss the histopathological aspects of Inflammatory Bowel Disease but also to demonstrate the interaction between the different specialisms, which reflects the multidisciplinary collaboration in our daily practice.