The first article of this series highlights information relating to the nature and treatment of IBD, which includes addressing the underlying inflammatory processes, as described in oral presentations given on Thursday 15 February — the first day of the plenary scientific programme and the parallel digital oral presentation sessions.
Looking into the aetiology of IBD, Dr Jonas Halfvarson and colleagues from Sweden performed a study that included 15 pairs of discordant twins and suggested the dysfunctional gut barrier is a primary defect in Crohn’s disease with a strong genetic component; dysbiosis (microbial imbalance) may be a consequence, rather than a cause, of inflammation. Assessing patterns of disease activity in the first ten years after diagnosis, data from a cohort of 432 patients with Crohn’s disease in the Netherlands, reported by Dr Dion Wintjens, showed that many patients may have a largely quiescent course of disease, which may be only moderately predicted by early clinical markers. Further research is required to identify markers more predictive of the disease course, and baseline stratification may help to avoid under- or over-treating patients.
Patient treatment was considered in another study from the Netherlands involving 170 patients with IBD who were aged 10–19 years and in clinical remission at baseline. Dr Patrick van Rheenen described how a telemonitoring strategy developed to recognise flares was shown to be “as safe as conventional follow-up”, appreciated by patients and their families, and cost-saving. Along similar lines, Dr Dorit Ankersen reported other results that supported the implementation of home monitoring. In a one-year open-label study of telemedicine, 120 adult patients in Denmark were randomised to home monitoring either “on-demand”, as patients felt it was needed, or every 3 months (combined with on-demand screening as patients considered necessary). Patients used a web application for home monitoring plus a faecal calprotectin home-testing kit. No differences in disease course were apparent between the two groups although compared to those in whom monitoring was performed at 3-monthly intervals, the on-demand group used less faecal calprotectin kits (mean per patient difference of 1.5), were less likely to drop out of the study (drop-out rates of 22% and 12%, respectively), and had increased disease-specific quality of life.
Presentations also considered the inflammatory processes underlying IBD, profiling of these, and ways in which inflammation may best be addressed to benefit patients.
Dr Magali de Bruyn and colleagues from Belgium evaluated changes in immune profiles, including serum markers of cell migration and immune response, in IBD patients treated with agents acting against different inflammatory targets. Different treatments produced specific changes in immune profiles. The results suggest that further clinical studies may be valuable to provide more information that might ultimately enable physicians to tailor therapeutic approaches for individual patients.
Continuing the theme of tailoring therapy, Dr Brecht Creyns (Leuven, Belgium) examined levels of different types of innate lymphoid cells (ILCs) in patients with IBD. These cells can produce cytokines at mucosal barriers and in IBD there may be an intestinal pro-inflammatory shift from ILC3 to ILC1. Results showed that increased baseline peripheral blood levels of ILC1 may predict non-response to therapy targeting the shared p40 subunit of IL-12 and IL-23. This might be explained by increased numbers of circulating pro-inflammatory ILC1s being available for migration to the intestine where they may counteract potential treatment effects.
Patients with ulcerative colitis have varying extents of colonic involvement in inflammation, with clear endoscopic demarcation between unaffected and affected areas. Analysis of colonic biopsies from affected patients showed “two striking patterns of gene expression”, according to a study performed by Dr Carmen Argmann (New York, USA) and colleagues. For some genes (“wall genes”), an abrupt change was apparent moving away from the inflammatory site. Other genes (“slope genes”) exhibited changing expression depending on the distance from the site of inflammation. Gradually decreasing expression of inflammatory slope genes, such as IL-6, suggests that inflammation may extend beyond that seen with endoscopy. Other slope genes, such as homeobox and solute carrier genes, were upregulated moving away from the inflammatory site, as were some wall genes, including those for fatty acid binding (FAB) proteins and glucoronidation. These changes are suggestive of changes in gut function. Understanding the complex molecular pattern involved here may provide information about the nature of ulcerative colitis and provide useful biomarkers.
While targeting of the α4β7 integrin is known to inhibit immune cell homing via effects on T lymphocytes in the gut, Dr Sebastian Zundler (Erlangen, Germany) presented data showing that this therapy may also inhibit homing of monocytes, which can regulate inflammation and remodelling of intestinal tissue via differentiation to M2 macrophages. With fewer M2 macrophages around mucosal wounds, healing may be impaired, and this might explain the occurrence of increased postoperative complications in patients receiving anti-α4β7 integrin antibody treatment.
Considering the benefits of targeting TNFα, Dr Anne Strik described results from a retrospective survey of 352 patients with Crohn’s disease in the Netherlands who had been treated with anti-TNF therapy. Data showed higher serum levels of anti-TNF to be associated with closure of perianal fistulae, suggesting dose reduction to be contraindicated in patients with perianal Crohn’s disease, even in those with quiescent luminal disease.
The value of using a panel of serum markers for detecting mucosal healing in anti-TNF treated patients with ulcerative colitis was shown by Dr de Bruyn, who described how neutrophil gelatinase B-associated lipocalin in complex with matrix metalloproteinase-9 (NGAL-MMP-9), cathelicidin LL-37, chitinase 3-like 1 (CHI3L1), C-reactive protein (CRP) and neutrophil count might have “broad utility” in such situations, exhibiting positive and negative predictive values of 67% and 92% respectively, with 75% sensitivity and 89% specificity when evaluating samples from 31 patients, 21 of whom (68%) achieved mucosal healing.
Interestingly, Dr Federica Ungaro (Milan, Italy) described how the early stages of gut inflammation may be influenced by specific eukaryotic viral infections, involving Hepadnaviridae in patients with ulcerative colitis and Hepeviridae in Crohn’s disease, suggesting that, if these viruses can be shown to be involved in triggering inflammation, specific antiviral drugs might have a future therapeutic role.
These presentations provide an idea of the value of the information available at the 13th Congress of ECCO. Further articles in this series will draw on discussions across the entire congress to help you appreciate the ways in which knowledge of IBD is continuing to advance.
European Crohn's and Colitis Organisation (ECCO) 2018. Programme available at: https://www.ecco-ibd.eu/images/2_Congresses_Events/2018/ECCO_programme18_final_web.pdf
Date accessed: 16 Feb 2018
The first article of this series highlights information relating to the nature and treatment of IBD, which includes addressing the underlying inflammatory processes.
As the theme for the 13th Congress of ECCO was “Science improving patients’ lives”, this article focuses on IBD patients as recent research suggests it is appropriate to consider patient perspectives of the condition.
This article discusses presentations from ECCO that provided insights into the nature of the immunological changes associated with inflammation as well as the genetic influences behind such changes.
This article describes highlights from selected oral presentations, showing how novel research may be pointing the way to improved treatment options for patients with IBD.
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