Randomised clinical trial: high‐dose oral thiamine versus placebo for chronic fatigue in patients with quiescent inflammatory bowel disease (TARIF study)
Fatigue is a common yet poorly understood manifestation of Inflammatory Bowel Disease (IBD) and can occur independently of disease activity. A prospective cohort study of 326 IBD patients initiating biologic therapy (with infliximab, vedolizumab or ustekinumab) demonstrated fatigue was prevalent at baseline (63%)1. Whilst fewer patients reported fatigue with treatment (70% at week 14, 61% at week 30 and 61% at week 54), a third continued to experience fatigue despite achieving clinical remission. This is supported by other studies, where fatigue prevalence in quiescent disease was as high as 36% in Ulcerative Colitis (UC) and 41% in Crohn’s disease (CD)2.
In the last decade, research on the human gut microbiome and its influence on health and disease has taken flight. This has strengthened the belief that the underlying pathogenesis of Inflammatory Bowel Disease (IBD) involves an altered immune response to characteristic shifts in the composition of the gut microbiome.
After a 2020 that ended up being all about COVID-19, let’s hope that 2021 will be a normal year where we can meet and network again and put COVID behind us. I recently got my first shot of the vaccination, which was a wonderful experience of what science is capable of in times of need. In Denmark we’ve started vaccinating our IBD patients but vaccine scepticism and uncertainties about the evidence is everywhere and we as physicians are needed more than ever to inform our patients.
Hemel is currently working as a dentist in London. He was diagnosed with Crohn’s Disease and within a year of getting his diagnosis he was invited to participate in a trial of an anti-TNF drug. Here he gives his view of his experience of being in a clinical trial.
Serum biomarkers identify patients who will develop inflammatory bowel diseases up to 5 years before diagnosis
Torres J, Petralia F, Sato T, et al.
Gastroenterology 2020;159:96–104.
Introduction
Inflammatory Bowel Disease is a chronic relapsing-remitting, immune-mediated condition with increasing prevalence globally [1]. Despite novel agents targeting different disease pathways, the likelihood of achieving sustained clinical remission and mucosal healing remains low [2]. One of the potential reasons may be that patients seek help and clinicians treat IBD once the disease is in its clinical phase. A sub-clinical phase of variable length may precede the symptoms that lead to a diagnosis and perhaps contribute to tissue damage which, once established, is difficult to reverse with currently available medical treatments.
In this study, Torres and colleagues set out to test the hypothesis that a pre-clinical phase of IBD may well be present and could be identified by proteomic markers [3].
Expression levels of 4 genes in colon tissue might be used to predict which patients will enter endoscopic remission after vedolizumab therapy for Inflammatory Bowel Diseases
Verstockt B, Verstockt S, Veny M, et al.
Clinical Gastroenterology and Hepatology. 2020;18:1142–51.
In the past few years the armamentarium of drugs used to treat Inflammatory Bowel Disease (IBD) has accelerated, with the emergence of new therapies targeting differing immune pathways (ustekinumab and tofacitinib) and lymphocyte trafficking (vedolizumab). Furthermore, a number of promising new drugs are on the horizon (JAK-1 inhibitors, IL23p19 antibodies and S1P inhibitors) [1, 2]. However, as the choice of drugs expands, so the uncertainty over which drug should be selected by the clinician also increases. Drug selection may be determined by a number of factors such as cost, mechanism of delivery (e.g. oral, intravenous or subcutaneous), presence of co-morbidities (such as malignancy or multiple sclerosis) and presence of extraintestinal manifestations. However, no drug is effective in all patients, with between 10% and 40% of patients suffering from primary and secondary loss of response [3–5].
Nowadays, IBD treatment not only targets symptomatic disease control but also aims to heal the intestinal mucosa [1] In Ulcerative Colitis (UC) there is mounting evidence that histological healing of the intestinal mucosa is associated with incremental benefit compared to endoscopic healing alone [2–8]. In a very recent meta-analysis of ten studies including 757 UC patients with complete endoscopic remission (Mayo Score 0 or equivalent) and with a minimum follow-up of >12 months, patients with histological remission had a 63% lower risk of clinical relapse (RR 0.37, 95% CI 0.24–0.56) than patients with ongoing microscopic inflammation [9].
I hope you had a nice UEG Week Virtual earlier in October. My experience with the many virtual symposia over recent months has been mixed, but I think that the virtual UEG Week worked very well, with great interactions from viewers and excellent lectures. Hopefully, we’ll be able to attend the ECCO Congress next year in person – I’m sure that you miss interacting with friends and colleagues as much as I do. But the experience at UEG Week makes me optimistic that this format can also work well.
At the 15th Congress of ECCO in Vienna, the Young ECCO Committee (Y-ECCO) and the Clinical Research Committee of ECCO (ClinCom) jointly conducted a survey of attendees entitled “Decision-making in IBD dysplasia management”. The results are currently being prepared for publication. This project followed on from other successful surveys which led to submission of abstracts at the ECCO Congress and publication of full manuscripts in scientific journals.
Britta Siegmund is Medical Director of the Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charité – Universitätsmedizin Berlin and holds many other important national and international roles within the scientific and medical communities. She has an extensive publication record in the mucosal immunology of IBD. She is also President-Elect of ECCO.
Johan Burisch
Charlotte Hedin 
