Emma Halmos © ECCO

Hannah Gordon © ECCO

Richard Hansen © ECCO

Diet in Inflammatory Bowel Disease has become a hot topic in recent years, pushed forward by advances in our understanding of the microbiome and the promise of nutrition as therapy, particularly in Crohn’s Disease. One of the most important questions in clinic (and yet the hardest to answer) remains “What can I eat?” or variations of the same. The reason this question is so difficult to answer is the enormous complexity in how diet overlays IBD and also the lack of high-quality scientific studies addressing this specific problem.

Iva Hojsak, who has recently joined the P-ECCO Committee, is a paediatric gastroenterologist and head of the Paediatric Department and deputy director of the Children's Hospital Zagreb, Croatia. Iva graduated from the Medical School of Zagreb, where she also received her PhD. She was subsequently elected as assistant professor at University of Zagreb Medical School and University of J.J. Strossmayer Medical School.

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?

Firas Rinawi © Firas Rinawi

Primary sclerosing cholangitis (PSC) is less common in paediatrics than in adults, affecting 0.2–1.5 per 100,000 children (~20% the prevalence in adults). Those diagnosed in childhood are typically older than ten years, and there is a male predilection [1]. The aetiology of PSC is likely a multifactorial combination of an inherited predisposition, gut microbiome, gut–liver communication, bile homeostasis and downstream effects on the immune system which lead to biliary inflammation and fibrosis [2].

In the last decade, numerous biologics and small molecules have been tested in clinical trials for patients with Crohn’s Disease (CD), and some have already been approved and used effectively in such patients. However, there is increasing interest in the use of dietary therapies for patients with CD from both providers and patients, who often wish to start an intervention that is not associated with immunosuppression. In addition, studies in both animal models and humans have put the spotlight on different dietary components that can either provoke or suppress intestinal inflammation. As an example, specific emulsifiers that are widely used in the food industry as preservatives increase the susceptibility of mice to develop colitis [1] and also alter the faecal microbiome and metabolome in humans characterised by pro-inflammatory perturbations [2].

Richard Hansen © ECCO

The risk of thrombosis in paediatric IBD has become a hot topic in recent months, prompted by the publication of two impactful papers in Journal of Crohn’s and Colitis [1, 2]. Kuenzig and colleagues presented a large Canadian population-based study which described a vastly increased thrombosis rate in children with IBD compared to the normal population: the 5-year incidence was 31.2 per 10,000 person-years among children with IBD versus 0.8 per 10,000 person-years among children without IBD (95% confidence intervals 23.7–41.0 and 0.4–1.7, respectively) [1].

Dror Shouval © ECCO

Over the past two decades, significant progress has been made in the understanding of the role of genetics in the pathogenesis of Inflammatory Bowel Disease (IBD): On the one hand, adult IBD studies have identified more than 250 single nucleotide polymorphisms that increase the risk of disease, though their individual and overall effect on the risk of developing IBD is small [1]. On the other hand, the expanding use of next-generation sequencing (NGS) platforms has resulted in the identification of more than 100 different rare monogenic disorders that directly cause IBD [2]. Given the central role of immune cells in sustaining immune tolerance in the gut, it is not surprising that in many cases monogenic disorders causing IBD result from pathogenic variants in genes involved in essential immune or epithelial pathways. Some patients with such disorders present with a clear immunodeficiency phenotype (e.g. chronic granulomatous disease, Wiskott-Aldrich syndrome), but in others IBD is the sole manifestation [3].

As the new chair of the P-ECCO Committee, it is my pleasure to introduce two newly elected members of the Committee: Richard Hansen and Dror Shouval, two wonderful paediatric gastroenterologists from Scotland and Israel, respectively. Both are very active in the paediatric IBD field and they bring a wealth of expertise and energy to our group.

In the last decade the traditional management of Inflammatory Bowel Disease (IBD), based on clinically guided treatment intensification, has been revised and the so-called treat-to-target (T2T) approach, focusing on objective and scheduled measures to monitor intestinal inflammation, has been implemented in clinical practice, both in adults and in children. The general idea behind such tight monitoring is to prevent or block intestinal damage related to persistent and uncontrolled inflammation, and to avoid long-term complications.

Anti-tumor necrosis factor alpha (TNFα) therapy is frequently used in the treatment of Crohn’s Disease (CD) and Ulcerative Colitis (UC) in both adult and paediatric patients. Nevertheless, primary or secondary treatment failure of anti-TNFα treatment is not uncommon [1]. Both primary and secondary treatment failures are attributed either to pharmacokinetic, pharmacodynamic and immunogenic factors or to adverse events in response to the specific agent [2]. In recent years, loss of response (LOR) during anti-TNFα treatment has commonly been approached through the use of therapeutic drug monitoring involving measurement of infliximab or adalimumab trough concentrations (TC) and anti-drug antibodies (ADAs). Therapeutic drug monitoring of anti-TNFα agents enables proper stratification of LOR into a specific type of LOR, with corresponding adjustment of treatment. In children, in line with findings in adults, it has consistently been shown that higher drug TC is associated with higher efficacy [3] and that LOR is most commonly attributable to either low TC or the development of anti-drug antibodies [4].