Submucosal injection of the RNA nucleotide GUT-1 in active ulcerative colitis patients: A randomized, double-blind, placebo-controlled phase 2a induction trial.

Atreya R, Kuhbacher T, Waldner M, et al.

J Crohns Colitis 2023. doi: 10.1093/ecco-jcc/jjad162. Online ahead of print.

Introduction

Despite an increasing number of therapeutic options for Ulcerative Colitis (UC), many patients still have disease which progresses over time, and there has been renewed interest in and improved understanding of the chronic fibrosis and remodelling that occurs in UC [1–3]. In particular, there has been a growing appreciation of both the importance of the extracellular matrix (ECM) for remodelling in UC and the potential to target the ECM with new therapeutic agents [4]. One such target is carbohydrate sulphotransferase 15 (CHST15). This is a type II transmembrane Golgi protein that biosynthesises highly sulphated disaccharide units (E-units) of chondroitin sulphate, which binds to various functional proteins and pathogenic microorganisms. Targeting this molecule in mouse models has previously been shown to offer promising signals for ameliorating colitis [5]. Based on this promising pre-clinical data, blockade of CHST15 has emerged as a potentially promising therapeutic target, and such blockade can be achieved by a silencing RNA oligonucleotide molecule called GUT-1 (previously called STNM01). A prior phase I clinical trial demonstrated the safety of GUT-1 in patients with Crohn’s Disease [6]. Accordingly, Atreya and colleagues now sought to evaluate the safety, as well as the efficacy and mode of action, of GUT-1 in patients with UC as part of a phase IIa placebo-controlled, clinical trial.

Upadacitinib induction and maintenance therapy for Crohn’s disease

Loftus Jr EV, Panes J, Lacerda AP, et al.

N Engl J Med 2023;388:1966–80. doi: 10.1056/NEJMoa2212728.

Introduction

The management of Crohn’s Disease (CD) is dependent on many factors, including disease activity, site of involvement and the need to tailor treatment for each individual patient [1]. Moreover, features such as obstruction, fistulation, strictures and abscesses can all add to the complexity of CD management. While surgery has played a large role in the management of these patients, it is by no means a cure and the risk of relapse and repeat surgeries remains high [2, 3]. Accordingly, there continues to be a large unmet need for the development of novel medications that target distinct mechanisms of action in order to provide symptomatic and endoscopic control for patients with active disease. In parallel with this need to develop new medications, there has been an increasing desire for fast-acting medications, and movement towards oral administration, which may help both to reduce costs for hospitals and patients and to enhance aspects that are important to patients, such as quality of life and work productivity [4, 5].

Intestinal barrier healing is superior to endoscopic and histologic remission for predicting major adverse outcomes in Inflammatory Bowel Disease: The Prospective ERIca Trial

Timo Rath, Raja Atreya, Julia Bodenschatz, et al.

Gastroenterology 2023;164:241–55

Introduction

Mucosal healing (MH) in both Crohn's Disease (CD) and Ulcerative Colitis (UC) has been recognised as an important treatment target for many years. Indeed, the 2021 update of the Selecting Therapeutic Targets (STRIDE) consensus reaffirmed MH as the top priority among long-term treatment objectives [1]. Nonetheless, it is important to note that endoscopic inflammation may not always mirror the histological picture. Histological healing is an emerging endpoint in IBD. This is particularly true in UC, in which it represents a deeper level of recovery with some early evidence for correlation with better long-term outcomes; for CD, however, findings have been more controversial [2, 3]. Despite the increasing focus on histology, histological scoring systems are complex, with only two validated ones, both in the setting of UC, i.e. there is no validated scoring system in the context of CD.

Dear Y-ECCO Friends,

I hope you are all well and that those of you who made the trip back to Copenhagen for UEGW had an interesting and enjoyable conference. We are now very much into the foothills of ECCO’24, which will take place in Stockholm in February, and I hope many of you have submitted your work for presentation there. I also hope that you will consider attending our 10th Y-ECCO Science Workshop, to be held on the afternoon of Wednesday, February 21, immediately prior to the main Congress itself. As always, we will have a mixture of established clinician-scientists presenting keynote lectures and up-and-coming Y-ECCO Members presenting their own original work. We’re looking forward to an inquisitive and collaborative atmosphere and it would be fantastic to see you all there!

Fibrosis and other connective tissue abnormalities are common in IBD, especially in Crohn’s Disease. The main clinical consequence is strictures, occurring most often in the small bowel or at the ileocaecal/ileocolic junction. Surgery may be necessary for stricture management.

Seamus Hussey © ECCO

2023 has been another outstanding year of emerging Inflammatory Bowel Disease (IBD) treatments – in adults.  Children and young adults remain underserved by clinical trials of IBD therapies.  While this age demographic garners much sympathy, and accounts for one-quarter of all new diagnoses, children and young adults are disenfranchised from accessing cutting-edge drug trials by virtue of age alone. Paediatric patients are the almost perfect participants – having generally fewer comorbidities, shorter disease duration and seemingly better treatment responses than adults. The additional challenges posed by trials in this age group have, however, left a relatively barren landscape of industry-sponsored trials in their wake. What, then, are the ongoing challenges, and what have industry and our drug trial community done to level the therapeutic playing field?

The increasing complexity of care for patients with Inflammatory Bowel Disease (IBD) has driven the need for multidisciplinary care.  This has led centres and practices to hold regular multidisciplinary team meetings (MDTs) at which specialists in gastroenterology, surgery, radiology and pathology discuss patients. It has also led to joint clinics where practice environments allow patients to be seen by specialists in both gastroenterology and surgery, and even in some cases by experts in stoma therapy, nutrition and psychology, all on the same day. This allows for greater cross-disciplinary dialogue and more consistent messaging to the patient, which improves the quality of care and overall patient experience.

As a D-ECCO Committee Member, it is my mission, along with my fellow D-ECCO’ers, to educate and train other dietitians and healthcare professionals in the field of IBD. Also, with dietary therapies and beliefs still growing and consolidating their place in the prevention and treatment of IBD, there is an emerging need for skilled dietitians to guide our patients in the different nutritional pathways throughout their disease. But what makes a dietitian skilled in the field of IBD?

General information

Name: Goedele Dewitte

Occupation: Nurse Consultant IBD

Observation period: 24–28 October, 2022

IBD location: St. Mark’s Hospital, Central Middlesex, London

Local Supervisor at St. Mark’s: Prof. Hart and ANP-IBD Nurse Madhoor Ramdeem

Supervisor at current IBD unit, Ghent University Hospital: Prof. Lobaton and Dr. Geldof

Goedele Dewitte © Goedele Dewitte

Background

St Mark's Hospital in London is the only hospital dedicated solely to gastrointestinal pathology. It includes a reference IBD unit, a world centre of excellence for endoscopy (Wolfson unit) and an intestinal failure/rehabilitation unit. Both the endoscopy and the intestinal rehabilitation unit work in harmony with the IBD unit to optimise the care for tertiary and complex IBD pathology.

This observational internship was intended to increase insight into the organisation of a tertiary, high-volume IBD reference centre from the nursing point of view.  

Torsten Kucharzik © ECCO

GuiCom has developed important and world-wide recognised guidelines on the Diagnosis and Management of IBD. In order to create standardised guidelines of the highest quality, regular rotation and recruitment of highly experienced candidates is crucial. It is my great pleasure to introduce Johan Burisch, who will become a new GuiCom Member at the beginning of 2024. Johan was selected from a large group of excellent applicants for this position.