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Background Diet is known to affect inflammatory bowel disease (IBD), but the optimal nutritional therapy during a severe flare is uncertain. The goal of this study was to describe variation in nutritional practices across Europe, between professions, types of hospitals and healthcare systems, as well as between ulcerative colitis (UC) and Crohn’s disease (CD). Methods A novel questionnaire comprising 17 questions, of which 5 concerning demographic data, was distributed digitally in the ECCO Congress 2022 and via the ECCO country representatives. In the comparisons of categories (e.g., countries), only categories with at least 25 responses were considered, and Chi-squared test was used. Results The survey was completed by 313 participants. Table 1 summarises their main characteristics. Physicians and dietitians were most commonly responsible for determining nutritional therapy for IBD inpatients (Table 2). The commonest form of nutritional therapy was oral nutritional supplements (ONS) on top of easy to digest food. Total parenteral nutrition (TPN) was used by 10% of respondents for UC patients and 7% for CD. Almost a quarter of respondents reported less than 25% of patients being assessed by a dietitian in the first 3 days of a flare. Energy intake, stool frequency and inflammatory biomarkers were the commonest factors to determine when to change nutritional therapy. No specific nutritional screening tool was used by 45% of respondents. There was significant variation between different European countries and healthcare professions for all the outcomes measured (p During the first three days of a severe flare, a diet consisting exclusively of ONS was significantly more frequently used for CD than UC (p=0.018, Figure 1). Otherwise, similar nutritional therapy strategies were reported for CD and UC including using TPN to a similar extent. Conclusion Country is the main determinant of differences in nutritional practice across Europe. Diet consisting exclusively of ONS is more common during a flare of CD than UC.

Background and Aims Alterations in the immunopathogenesis in ulcerative colitis [UC] during the disease course have been proposed. We therefore aimed to determine mucosal and systemic immune profiles in individual patients at the time of diagnosis [early disease] and after 10 years [late disease]. Methods Patients with UC provided serum and mucosal biopsies during a flare in early and in late disease. Serum samples were analysed using the Olink Proseek Inflammation panel. mRNA gene expression of biopsies was analysed using the Qiagen RT2 Profiler PCR Arrays Antibacterial response and T Helper Cell Differentiation. Results Orthogonal projections to latent structures discriminant analyses [OPLS-DA] demonstrated that the profile of 15 serum proteins discriminated in early and late disease [R2 = 0.84, Q2 = 0.65] in 15 UC patients. Eight of these proteins were differently expressed between the groups [Q Conclusions Mucosal and systemic immune profiles differ between early and late disease in patients with active UC, with a transition from a Th1- to a Th2-driven disease in the intestine. Improved understanding of the variation in immunopathogenesis during the disease course in UC is important to guide individualised treatment decision making.

Background Clinical trials may not readily reflect clinical practice. We aimed to assess the clinical effectiveness of vedolizumab in a real-world cohort of patients with ulcerative colitis (UC). Methods This is a prospective, observational, multi-centre cohort study. Eligible patients had active UC confirmed by a Mayo endoscopic subscore ≥2 at initiation of vedolizumab and had started treatment from 1/6/2015. Exclusion criteria included concurrent participation in a clinical trial in which UC treatment is dictated and contraindications to vedolizumab. All patients provided a written consent. Data on clinical characteristics, treatment patterns, disease activity and the short health scale were recorded at baseline and prospectively, using an electronic Case Record Form, integrated with the Swedish National Quality Registry for IBD (SWIBREG). The primary outcomes were A) clinical response, defined as a decrease in partial Mayo score of ≥2 and a reduction of ≥25 % from baseline, with a decrease ≥1 on the rectal bleeding score or an absolute rectal bleeding score of 0 or 1, at week 12 and B) clinical remission, defined as a partial Mayo score Results In total, 117 eligible UC patients were included during the study period 1/6/2015 to 2/6/2018. Clinical and demographical characteristics of patients are shown in Table 1; 101/117 (86%) patients had failed prior anti-TNF therapy. The drug persistence rate was 106/117 (91%) at 12 weeks and 79/117 (68%) at 52 weeks. The clinical response rate at 12 weeks was 59/117 (50%) and the clinical remission rate at 52 weeks was 57/117 (49%). Altogether, 35/117 (30%) had an endoscopic Mayo score ≤1 at 12 weeks and 41/117 (35%) at 52 weeks. However, data on endoscopy were not available for 42 vedolizumab treated patients at 12 weeks and 30 at 52 weeks. Among patients who continued vedolizumab, the median partial Mayo score decreased from 4 (3–5) at baseline to 1 (0–2) at 52 weeks (p < 0.0001). Correspondingly, the median faecal calprotectin decreased from 646 (333–1130) µg/g to 162 (42–382) µg/g (p = 0.0002) and the median C-reactive protein from 5.0 (2.1–8.0) mg/L to 3.5 (1.6–5.0) mg/L (p = 0.008). Consistently, quality of life improved in vedolizumab treated patients, with a significant reduction of the overall short health scale score at 52 weeks (p < 0.0001). Conclusion Vedolizumab treated patients with UC represented a treatment-refractory group. Long-term (52 weeks) effectiveness of vedolizumab can be achieved, in terms of clinical- and inflammatory activity as well as in quality of life. The study was financially supported by Takeda.

The global prevalence of cancer is increasing, largely as more patients are living into old age. Therefore, gastroenterologists caring for patients with inflammatory bowel disease [IBD] increasingly are managing patients with cancer, or a previous history of cancer. This often requires joint management with the patient’s oncologist, enabling case-by-case decision-making based on the characteristics and expected evolution of the index cancer. Previously, no European guidelines existed describing the impact of IBD on malignancy. For this reason, the European Crohn’s and Colitis Organisation [ECCO] Guidelines Committee [GuiCom] decided to elaborate a set of Consensus Statements on optimal risk/benefit strategies for treating IBD patients with cancer or a history of cancer. The development of clinical practice guidelines is expensive and time consuming, and it is the Committee’s hope that these statements will facilitate and accelerate future efforts to elaborate formal guidelines, providing useful information on areas for which evidence is lacking and where controlled studies are needed. The strategy used to produce the Consensus Statements involved five steps: 1. Two members of Guicom [VA and RE] identified four main topics that needed to be addressed: a] IBD and solid tumours; b] IBD and skin and haematological malignancies; c] malignancy related to therapy: risk and prevention; and d] management of IBD patients with a history of malignancy. During 2014, calls for participation in the drafting of consensus statements were issued to ECCO members, and selected oncologists known for their expertise and active research in the field were invited to join the Consensus. Participants were selected by the Committee, and four working groups were created, each composed of a chairperson [LE, RE, LB, and VA], two ECCO members including young members [Y-ECCO], and one or two experienced oncologists. The chairmen and their groups elaborated relevant questions on topics dealing with current practice and/or areas …

Anti-tumour necrosis factor [TNF] therapy is used in patients with ulcerative colitis [UC], but not all patients respond to treatment. Antimicrobial peptides [AMPs] and the gut microbiota are essential for gut homeostasis and may be important for treatment outcome. The aim of this study was to determine AMP and microbiota profiles in patients with UC before anti-TNF therapy start and correlate these data to treatment outcome.Serum and biopsies were obtained from UC patients naïve to biological therapy [n = 56] before anti-TNF therapy start [baseline]. Fecal samples were taken at baseline and Weeks 2 and 6. Quantitative proteomic analysis was performed in mucosal biopsies. Expression of AMPs and cytokines was determined in biopsies and serum. Microbiota analysis of fecal samples was performed using GA-map™ Dysbiosis Test and real-time quantitative polymerase chain reaction [rtPCR]. Treatment response was evaluated 12-14 weeks after baseline.At baseline, proteomic analysis of biopsies showed that treatment responders and non-responders had differential expression of AMPs. Eleven AMP and AMP-related genes were analysed by rtPCR in mucosal biopsies and could together discriminate responders from non-responders at baseline. The most important nominators for response were increased expression of defensin 5 and eosinophilic cationic protein. Microbiota analysis revealed lower dysbiosis indexes and higher abundance of Faecalibacterium prausnitzii in responders compared with non-responders at baseline. Also, abundance of F. prausnitzii increased during induction therapy in responders.Anti-TNF therapy responders and non-responders display distinctly separate patterns of mucosal AMP expression and gut microbiota before treatment start. This indicates that intestinal antimicrobial/microbial composition can influence treatment outcome.

Background and aims: Symptoms compatible with irritable bowel syndrome (IBS) are common in patients with ulcerative colitis (UC) in clinical remission. It has been suggested that these symptoms might arise due to post-inflammatory changes comparable with post-infectious IBS. The aim was to study factors at new onset of UC that predict development of IBS-like symptoms during clinical remission. Methods: In total, 98 patients with new onset of UC were followed prospectively for 3 years with yearly follow-up visits. Data from the first visit at the onset of UC were compared between a group of patients who fulfilled the criteria for IBS while in remission (UCR+IBS) during follow-up and a group who did not (UCR–IBS). Results: Among the UC patients, 87 met the criteria for clinical remission and 25 (29%) of these reported IBS-like symptoms in remission during follow-up. There was no difference in inflammatory disease activity at the initial flare or in the prevalence of previous IBS symptoms when comparing UCR+IBS and UCR–IBS patients. The UCR+IBS patients reported more severe gastrointestinal symptoms, including abdominal pain, during their primary flare. Conclusion: The severity and extent of inflammation at onset of UC do not seem to affect the development of IBS-like symptoms in UC patients during clinical remission. The high prevalence of IBS-like symptoms is not explained by pre-existing IBS. UCR+IBS patients reported more severe gastrointestinal symptoms at disease onset, which might indicate a more sensitive gastrointestinal tract in this category of patients.

Background and aims: The cellular mechanisms leading to infliximab therapy response in patients with ulcerative colitis (UC) are incompletely known. We therefore investigated early effects of infliximab therapy on monocytes and associated chemokines linked to clinical therapy response in UC patients. Methods: Blood and biopsies were obtained from anti-TNF therapy-naive UC patients ( n = 43) before (baseline) and during induction therapy with infliximab. Therapy response was evaluated at Week 14. Expression of monocyte activation markers and levels of chemokines in serum and biopsies were determined. Quantitative proteomic analysis was performed in cultured mucosal biopsies, and obtained data was validated in serum. Results: In therapy responders, but not in non-responders, infliximab reduced blood monocyte expression of CD14 and CD86, 2 weeks after therapy commenced, relative to baseline. Serum CCL2 levels were decreased only among therapy responders at Week 2 and Week 14, relative to baseline. These data corresponded with lower levels of CD14, CD86 and CCL2 in intestinal tissue in responders as compared with non-responders at Week 14. Proteomic analysis of cultured biopsies showed that infliximab induced a reduction in Tenascin C that predicted downregulation of CCL2. Therapy responders, but not non-responders, had decreased serum Tenascin C levels at Week 2 and Week 14, relative to baseline. Conclusions: Infliximab therapy response in UC patients is associated with reduced monocyte activation and serum levels of CCL2 2 weeks after therapy commencement. In therapy responders, infliximab influenced Tenascin C, which might be a regulator of CCL2 expression and important for induction of the clinical therapy response. * Abbreviations: : UC : ulcerative colitis IBD : inflammatory bowel disease TNF : tumor necrosis factor ECM : extracellular matrix TNC : Tenascin C PBMC : peripheral blood mononuclear cell MS : mass spectrometry IPA : ingenuity pathway analysis IPA KB : Ingenuity Pathways Analysis Knowledge Base MAP : molecule activity predictor

Background and Aims Ileocaecal resection for Crohn's disease is commonly performed. The severity of endoscopic lesions in the anastomotic area one year postoperatively is considered to reflect the subsequent clinical course. Fecal calprotectin (FC) has been shown to correlate with the findings at ileocolonoscopy in Crohn's disease. The objectives of this study were to assess whether the concentration of FC reflects the endoscopic findings one year after ileocaecal resection and to evaluate the variation of FC in individual patients during 6 months prior to the ileocolonoscopy. Methods Thirty patients with Crohn's disease and ileocaecal resection performed within one year were included. Stool samples were delivered monthly until an ileocolonoscopy was performed one year postoperatively. Results One year after surgery the median values of FC were not significantly different between the patients in endoscopic remission (n = 17) and the patients with an endoscopic recurrence (189 (75–364) vs 227 (120–1066)μg/g; p = 0.25). However, most patients with low values were in remission and all patients with high (> 600 μg/g) calprotectin values had recurrent disease. The variability of the FC concentration was most pronounced in patients with diarrhea. Conclusions We found no statistical difference in the concentrations of calprotectin between patients in endoscopic remission and patients with a recurrent disease one year after ileocaecal resection for Crohn's disease. However, among the minority of patients with low or high values, FC indicated remission and recurrence, respectively. There was significant variation of the fecal calprotectin concentrations over time, which affects the utility of calprotectin in clinical practice.

Clinical effectiveness of golimumab : Interim analysis of the observational study of patients with ulcerative colitis on golimumab in the Swedish National Quality Registry for IBD-GO-SWIBREG

Clinical effectiveness of vedolizumab : Interim analysis of the Swedish observational study on vedolizumab assessing effectiveness and healthcare resource utilisation in patients with ulcerative colitis (SVEAH UC)

Background Little is known of the importance of chromogranins (Cg) and secretogranins (Sg) in ulcerative colitis (UC). We therefore investigated fecal levels of CgA, CgB, SgII and SgIII, and their association with inflammatory activity, disease duration and medical therapy in UC. Methods Analyses of CgA, CgB, SgII, SgIII and calprotectin in stool samples from 41 UC patients and 29 healthy controls were performed. Two stool samples, during relapse and remission, respectively, were obtained from each UC patient. Results The levels of fecal CgA and SgII were higher in UC patients with active disease as compared to healthy controls. CgB and SgII were positively correlated with disease duration, but none of the granins were positively correlated with calprotectin, Mayo score, CRP or serum concentrations of TNF in UC patients with active disease. Also UC patients in remission had higher levels of CgA, CgB, SgII, and SgIII as compared to healthy controls. However, levels of fecal CgA, CgB, SgII and SgIII were lower during active disease relative to remission. Moreover, fecal levels of CgA and SgII were higher in UC patients in remission treated with thiopurines than in thiopurine-naive patients in remission. Conclusion Fecal chromogranins and secretogranins are increased in UC but are not associated with disease activity, but seem to increase with duration of the disease. Thus, fecal granins might reflect structural changes associated with chronicity of disease, or medical therapy.

A Swedish observational study (SVEAH) on vedolizumab assessing effectiveness and healthcare resource utilization in patients with inflammatory bowel disease

This ECCO Topical Review of the European Crohn's and Colitis Organisation [ECCO] focuses on the role of environmental factors with respect to the development of inflammatory bowel disease [IBD] as well as their influence on the course of established IBD. The objective was to reach expert consensus to provide evidence-based guidance for clinical practice.

inflammatory bowel disease (IBD). Only limited data are available about the diagnostic accuracy of fecal matrix metalloprotease (MMP)-9 in IBD. The aims of our prospective study was to assess the diagnostic accuracy of fecal MMP-9 in patients with active Crohn’s disease (CD), ulcerative colitis (UC) and pouchitis assessed by clinical, endoscopic and histological scores and to compare the diagnostic accuracy of fecal MMP-9 and fecal calprotectin (CP) in IBD. Methods: Stool and blood samples were collected in 52 CD, 34 UC and 33 ileal pouch-anal anastomosis patients before control endoscopy. Biopsies were taken for histology. The activities of CD, UC and pouchitis were defined with the use of clinical, endoscopic and histological activity scores (CDAI, partial Mayo score, PDAI, SES-CD, Mayo endoscopic subscore, D’Haens and Riley score). Fecal CP and MMP-9 levels were quantified by use of enzyme-linked immunosorbent assay. Results: Active CD, UC and pouchitis was detected in 33.9%, 58.8% and 30.3% of the patients. Significant correlation was shown between the clinical, endoscopic and histological activities and fecal MMP-9 concentration in UC and pouchitis. Fecal CP concentration did not correlate with the clinical, endoscopic and histological activities of either UC or pouchitis. In CD, fecal CP correlated with the clinical, endoscopic and histological activities of the disease, and although fecal MMP9 concentration did not show significant correlation with SES-CD, stronger correlation was observed than in case of CP considering the clinical and histological activities of CD. Conclusions: This is the first study assessing the diagnostic accuracy of MMP-9 in different types of IBD. Our results showed that fecal MMP-9 has an exclusively high specificity in the detection of active UC and pouchitis and it also correlates stronger than fecal CP with the clinical and histological activities of CD. Further studies are needed to confirm these results.