Crohn's Disease (CD) is an idiopathic Inflammatory Bowel Disease (IBD) characterised by transmural inflammation of the affected tracts. The uncontrolled inflammation can lead to bowel damage, defined as the onset of strictures, abscesses or fistulas negatively impacting patients' quality of life and outcomes. The Lémann index (LI) is a recently validated tool that was specifically designed to assess the presence of penetrating or stenosing lesions and to quantify their severity. LI is a complex and time-consuming score which is based on imaging [magnetic resonance imaging (MRI)] and endoscopic procedures. Of note, it is mainly used in clinical trials, while its use in clinical practice is limited. Our aim was to develop a simplified LI and to compare the correlation between this simplified LI and the standard LI in assessing bowel damage.
Inflammatory Bowel Diseases (IBD) are devastating diseases induced by a breakdown of gut homeostasis, in which CD4+ effector T cells are major mediators of the inflammatory response. Interestingly, CD4+ effector T cells can convert into regulatory T cells, thereby controlling inflammation. However, the forces driving this T-cell plasticity remain largely unexplored, especially in IBD patients. In this regard, changes in the microbiota that can induce different T-cell profiles are commonly observed during IBD. The present proposal aims to elucidate how CD4+ T-cell plasticity can be modulated from a pro-inflammatory towards an anti-inflammatory profile in IBD patients. Our hypothesis is that the microbiota may modulate T cells towards an anti- or pro-inflammatory profile. To address this issue, we aim to analyse T-cell plasticity in IBD patients and mouse IBD models, and to correlate our findings with the microbiota composition. Furthermore, we will study whether antibiotics commonly used to treat IBD affect T-cell plasticity through microbiota-dependent processes.
Britta Siegmund is Medical Director of the Medical Department, Division of Gastroenterology, Infectiology and Rheumatology at the Charité - University Hospital Campus Benjamin Franklin Berlin, Germany. She has recently been accredited with the position of the new President-Elect of ECCO and we were happy to conduct an exclusive interview with her.
For the convenience of our ECCO News readers we recorded the interview and put it in an audio file. We hope you will enjoy listening to interesting facts about our President-Elect.
Glen Doherty is a consultant gastroenterologist at the Centre for Colorectal Disease at St Vincent's University Hospital and University College Dublin (UCD) as well as Research Director of the Centre for Colorectal Disease. In addition, he serves as an Executive Board member of the Irish Society of Gastroenterology (ISG). He joined GuiCom in 2016 and has been the chair for the last year.
The anti-TNF monoclonal antibody infliximab offers an effective treatment for patients with Inflammatory Bowel Disease (IBD) refractory to conventional immunomodulator therapies. Successful biologic therapy can lead to clinical and endoscopic remission as well as reduced hospitalisation and requirement for surgery [1].
Unfortunately, as a large protein and chimeric antibody, infliximab is immunogenic and this frequently leads to formation of anti-drug antibodies (ADA), with subsequent secondary loss of response (LOR), drug discontinuation and adverse reactions [2]. Identifying patients at increased risk of developing antibodies prior to treatment may establish which individuals require closer drug level monitoring, concomitant immunomodulator therapy and observation for adverse events.
Previous work by Sazonovs et al. identified the first genetic locus to be robustly associated with immunogenicity to anti-TNF therapies [3]. The HLADQA1*05 allele variant rs2097432, carried by approximately 40% of Europeans, significantly increased the rate of formation of infliximab ADA. In the study reviewed here, Wilson et al. aimed to independently identify whether presence of the variant allele was associated with increased risk of ADA formation, LOR, drug discontinuation and adverse events.
Perianal fistulising Crohn’s Disease is a challenging phenotype affecting more than 20% of patients diagnosed with Crohn’s Disease. It is associated with debilitating symptoms and significant morbidity, with subsequent reduced quality of life and increased disease-related work disability.
Currently treatment remains challenging, incorporating surgical and medical management; the latter is driven largely by biologic agents, specifically anti-tumour necrosis factor (TNF) agents such as adalimumab (ADA) and infliximab (IFX). Whilst ADA and IFX have proven efficacy in inducing and maintaining fistula healing and closure, a significant proportion of patients fail to respond or lose response over time. Increasing evidence suggests that this is in part due to sub-therapeutic drug levels, with or without the presence of antibodies to anti-TNF agents (ATA), with higher target drug levels required for fistula healing compared to mucosal healing in Crohn’s Disease. However, data evaluating the correlation between anti-TNF levels and perianal fistula outcomes, particularly with ADA, remain limited.
The aim of this study was to assess the association between anti-TNF levels and perianal fistula healing and closure with maintenance ADA and IFX therapy.
Pre-treatment frailty is independently associated with increased risk of infections after immunosuppression in patients with Inflammatory Bowel Diseases
Kochar B, Cai W, Cagan A, Ananthakrishnan AN
Gastroenterology 2020 Feb 25;S0016-5085(20)30243-2. doi: 10.1053/j.gastro.2020.02.032. Online ahead of print.
The growing arsenal of therapies available for Inflammatory Bowel Disease (IBD) is improving IBD physicians’ ability to target remission. However, risk of infectious complications associated with immunosuppression is a reality that weighs in the minds of physicians and patients alike, affecting the acceptability of these treatments [1]. Both treatment- and patient-related risk factors for infection have been identified in observational studies. Systemic steroids and combination anti-tumour necrosis factor (anti-TNF) and immunomodulator therapy are particularly associated with increased risk of infection, while non-modifiable patient factors include older age and non-IBD comorbidities [2–4]. Accordingly, this perceived risk results in reduced use of effective therapies in older people, despite risk of disease progression and a need for surgery similar to that in young people [5,6].
As explained by Kochar et al., however, chronological age does not capture the physiological heterogeneity in older populations, possibly leading to treatment being unnecessarily conservative in some. Furthermore, reliance on chronological age may lead to underappreciation of risk in younger people. Accordingly, more accurate tools for risk stratification of patients in the setting of immunosuppressive therapies are required.
How the world has changed during these last couple of months!
I hope you are all doing well despite the circumstances and are coping with the changes in workload, day-to-day activities and research that the pandemic has forced upon us. Also, many Y-ECCOs will have seen their educational programmes and training placed on hold. In Denmark, we have started opening society again since May and the number of infected persons is decreasing. However, there is still a lot of uncertainty about the consequences for society and the health care system. How are things in your country?
Dietary advice in the management of IBD has evolved in recent years from having gastrointestinal symptom reduction as a goal to a more pathogenesis-focussed approach [1–4]. At present, dietary recommendations in adult Crohn’s Disease (CD) are limited to increasing dietary fibre by means of fruit and vegetables and decreasing processed foods [1]. The nutrition debate has long divided adult and paediatric CD care, from international guidelines all the way through to service provision arrangements, with growth failure being a common feature in paediatric CD and dietetic support being a mainstay of care in many children’s hospitals [5–7].
As the new chair of the H-ECCO Committee, it is my pleasure to introduce our two newly elected members for 2020, Ann Driessen and Pamela Baldin, who are both Belgian pathologists. Thus, the current members of the H-ECCO Committee are: Monika Tripathi (Addenbrooke’s Hospital, Cambridge, UK), Francesca Rosini (Imperial College Healthcare NHS Trust, London, UK), Ann Driessen, Pamela Baldin, and myself, Gert De Hertogh (University Hospitals KULeuven, Belgium).
Ferdinando D'Amico
Andres Machicote
Ignacio 
Charlotte Hedin 
Johan Burisch
