ECCO News Editors’ Summary of the top 10 DOPs at ECCO'21 Virtual

   Summary of top 10 DOPs                                  

The winners of the Top 10 DOP awards are

DOP07: Ulcerative Colitis associated single nucleotide polymorphisms found in transcription factor binding sites effect key pathogenesis pathways and facilitate patient stratification

Dezso Modos, Ely, United Kingdom

In this innovative study, Modos et al. presented an update method to analyze the functional role of single nucleotide polymorphisms (SNP) in patients with Ulcerative Colitis, called iSNP.

The investigators found 15 UC-associated SNPs which affected transcription factor binding sites and were modulating 54 genes. Notably, the authors could identify five clusters of patients that correlated with therapeutic escalation defined by mesalazine or other more advanced therapy. In addition, the investigators were able to predict that those UC patients who have a vascular endothelial growth factor (VEGF)-affecting SNP – RS943072(G) – will require therapeutic upscaling. This approach may help to improve the use of genetics in precision medicine in the field of IBD and stimulate the exploration of new mechanistic studies.

DOP14: Ultra-high magnification endocytoscopy and molecular markers for defining endoscopic and histologic remission in Ulcerative Colitis

Marietta Iacucci, Birmingham, United Kingdom

Defining deep remission is still challenging in IBD.

Iacucci et al. presented the results of their study aiming to define deep remission using ultra-high-magnification endocytoscopy (520-fold) during colonoscopy and histological indices. In addition, the authors assessed cellular architecture, expression of molecular markers and their correlation with endoscopic scores in 29 UC patients.

A very good correlation was found between an endocytoscopy score and the histological indexes (Nancy and Robarts), showing its diagnostic potential. In addition, ultra-high-magnification endocytoscopy could identify gene expression markers and pathways that are also detected by histology (e.g. genes relevant to TGF-β signalling, macrophage recruitment into tissues, neutrophil and plasma cell function, and tumour suppression).

This work underscores the potential of high-magnification endocytoscope to define deep remission in Ulcerative Colitis.

DOP19: Urinary metabolome in newly diagnosed treatment-naïve Crohn’s Disease patients: Results from the IBDomics study

Laila Aldars-García, Madrid, Spain

In this study, Aldars-García et al. explored the role of the urinary metabolome in 131 newly diagnosed treatment-naïve Crohn’s Disease (CD) patients and its potential use to identify the metabolic profile related to the different CD subtypes.

The authors identified several metabolites that were differently abundant in CD patients with respect to controls and in different CD clinical settings. These metabolites were involved in relevant processes related to energy and amino acid metabolism.

The analysis of urinary metabolites could help to elucidate some aetiopathological mechanisms in CD and lead to the discovery of potential biomarkers.

DOP36: Non-invasive assessment of postoperative disease recurrence in Crohn’s Disease: A multicenter, prospective cohort study

Federica Furfaro, Rozzano, Italy

Early prevention of postoperative recurrence in Crohn’s Disease is key in order to avoid complications. Here, Furfaro et al. explored a combination of non-invasive parameters for early diagnosis of recurrence.

Using a combination of bowel ultrasound and faecal calprotectin, the investigators showed that the presence of increased bowel wall thickness, the presence of lymph nodes on ultrasound and faecal calprotectin >50 µg/g were independent predictors for endoscopic recurrence.

The authors conclude that combined use of bowel ultrasound and faecal calprotectin is accurate in assessing endoscopic recurrence 6 months after surgery and represents a valid alternative to endoscopy.

DOP41: Temporal trends in the epidemiology of Inflammatory Bowel Diseases in the public healthcare system in Brazil: A large population-based study

Abel Quaresma, Joaçaba, Brazil

Quaresma et al. presented the results from a large population-based epidemiological study on the incidence and prevalence of Inflammatory Bowel Diseases (IBD) in Brazil.

A total of 212,026 IBD patients were included. The authors found a higher proportion of females diagnosed with IBD and showed stable incidence rates in recent years (2012–2020).

Interestingly, the researchers found an opposite tendency in the incidence of UC and CD. While the incidence of CD is significantly decreasing in Brazil, that of UC is significantly increasing. The estimated prevalence of IBD has increased significantly (from 30.01 per 100,000 in 2012 to 100.13 per 100,000 in 2020).

The authors pointed to the impact of the increasing prevalence of IBD on the national healthcare system and the need for adequate resources to achieve optimal care.

DOP52: Safety of Inflammatory Bowel Disease drugs during pregnancy and breastfeeding: Mothers and babies’ outcomes (DUMBO registry)

Maria Chaparro, Madrid, Spain

Chaparro et al. presented the results from a Spanish national multicentre registry designed to assess the risk of serious adverse events both in mothers exposed to IBD drugs during pregnancy and in children up to 4 years of age who have been exposed to IBD drugs during pregnancy.

A total of 433 women and 237 newborns were included. In the multivariate analysis adjusted by disease activity, neither immunosuppressants nor biologics, as monotherapy or combination therapy, were associated with higher risk of severe adverse events compared with the non-exposed group.

However, the authors reported that a quarter of women with IBD suffered severe adverse events during pregnancy and 17% needed hospitalisation, highlighting the need for appropriate care of IBD women during pregnancy.

DOP62: Immunogenicity to second anti-TNF therapy (IMSAT): Implications for sequencing of biologic therapy

Neil Chanchlani, Exeter, United Kingdom

Anti-TNF treatment failure is a common phenomenon in the management of IBD patients and may require rescue with a second anti-TNF.

In this study, Chanchlani et al. explored the risk of immunogenicity to a second anti-TNF and the rates of drug persistence to a second anti-TNF in a retrospective cohort study across 32 UK hospitals including 870 patients. Immunogenic failure was defined as treatment failure with suboptimal drug levels and high antibody levels and pharmacodynamic failure was defined as treatment failure despite adequate drug levels.

The authors showed that immunogenicity to the first anti-TNF was associated with immunogenicity to the second anti-TNF, irrespective of drug sequence. Of note, starting an immunomodulator at the time of switching to second anti-TNF was associated with improved drug persistence in immunogenic but not pharmacodynamic failure.

Half of the patients remained on a second anti-TNF at 5 years independently of the cause of treatment failure, which led the investigators to conclude that switching within an anti-TNF class may be appropriate irrespective of the cause of failure to first anti-TNF.

DOP64: Endoscopically injected allogeneic mesenchymal stromal cells alter the mucosal immune cell compartment in patients with ulcerative proctitis

Laura Ouboter, Leiden, The Netherlands

Local injection of mesenchymal stromal cell (MSCs) is an approved therapy for the treatment of Crohn’s Disease-associated perianal fistulas

In this work, Ouboter et al. evaluated engraftment and immunoregulatory effects of this therapy in patients with refractory ulcerative proctitis by analysing biopsies and serum before and after treatment.

Thirteen UC patients with refractory proctitis were included. Complete remission was not achieved, but the investigators reported a significant improvement in Mayo score.

Injection of MSCs improved the immunological profile of patients (increase in a subset of effector memory CD4+ cells and several myeloid subsets), providing new evidence for the mechanism of action of MSC therapy on rectal mucosa. Interestingly, new anti-HLA class antibodies developed in 2/13 patients after local administration, which might influence donor selection.

DOP73: Antibiotic use differentially affects the risk of antidrug antibody formation during anti-TNF therapy in Inflammatory Bowel Disease

Yuri Gorelik, Haifa, Israel

Anti-drug antibodies (ADA) to anti-TNFα therapy drive loss of response to treatment in a significant proportion of IBD patients. In this study, Gorelik et al. aimed to assess the possible implications of specific antibiotic treatments on ADA formation in patients with IBD.

The authors analysed retrospectively 1,946 patients treated with anti-TNF therapy (positive ADAs were detected in 363). Kaplan-Meier curves of prior antibiotic use demonstrated a significant risk of ADA development in patients who used cephalosporins or penicillins with beta-lactamase inhibitors and reduced risk with prior use of fluoroquinolones, macrolides or metronidazole.

In addition, a sub-study showed that in mice exposed to infliximab, there was increased ADA production by cefuroxime treatment and a non-significant reduction in ADA following azithromycin treatment.

The authors conclude that ADA production is microbial dependent and suggest that the risk of ADA development during anti-TNF therapy can possibly be reduced by treatment with fluoroquinolones or macrolides or by avoidance of certain antibiotics such as cephalosporins and penicillins with beta-lactamase inhibitors.

The clinical implications of these findings need to be studied in large prospective trials but they may change the use of antibiotics in this clinical setting.

DOP87: Disease clearance as a new therapeutic target in patients with Ulcerative Colitis: A multicenter retrospective cohort study

Ferdinando D'Amico, Rozzano, Italy

Traditionally, symptom control and mucosal healing have been the main treatment endpoints in Ulcerative Colitis. In this work, D’Amico et al. explored the concept of disease clearance (a new outcome that simultaneously takes into account remission of symptoms, endoscopy and histology) and its impact on long-term outcomes in patients with UC.

A total of 302 patients were included in this multicentre retrospective cohort study. Disease clearance was defined as clinical (partial Mayo score ≤2 with no subscore >1), endoscopic (endoscopic Mayo score= 0) and histological (Nancy index= 0) remission. Disease clearance was measured at baseline and during follow-up. This was done by comparing if patients achieved negative disease outcomes.

The group with disease clearance at baseline experienced a significantly lower rate of hospitalisation and surgery compared with patients with endoscopic and/or histological disease activity. The authors conclude that these results may support the use of disease clearance as the ultimate therapeutic goal in UC patients in the near future.