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Educational objectives:
- To know the main nursing intervention in caring and management of patients with IBD
- To review the evidence about the impact of these interventions on patients' outcomes
- To have an overview of the methodology that will be used in this project: the network meta-analysis

Summary:
Specialist nurses dedicated to the care and management of patients with Inflammatory Bowel Disease (IBD) are increasing in number and roles across Europe. Despite the increased interest in the opportunities connected to this emerging healthcare professional, both from patients’ and clinicians’ perspectives, scarce evidence is available on the effectiveness of specialist nursing interventions. A deep review of the impact of specialist nursing interventions on the management and care of patients with IBD, especially on their health-related (HR) quality of life (QoL), is needed.
The main aim of this project is to systematically review studies assessing the impact of specialist nursing interventions in improving care and management of IBD patients and their QoL.
This project also aims to:
- identify which skills and types of nursing interventions should be developed to respond more effectively to patients' health needs;
- assess the effects of nursing interventions also on different outcomes such as (i) the proportion of patients entering remission, (ii) the proportion of patients in whom remission is maintained, (iii) the duration of remission, (iv) patients’ compliance and satisfaction, (v) number/rate of hospital admissions, (vi) costs savings.

These objectives will be reached through the conduction of  a systematic review and network meta-analysis.

With the grant of the NECCO we started at the Erasmus MC sophia children's hospital a multicenter study into validation of the Transition Success Score (TSS). The TSS was developed using an international Delphi procedure (van den Brink; 2019). Hopefully after this validation study the TSS can be used to measure the success/failure of transition in care.

Although the current doctrine of IBD pathogenesis proposes an interaction between environmental factors and gut microbiota in genetically susceptible individuals, dietary exposures have attracted recent interest and are, at least in part, likely to explain the rapid rise in disease incidence and prevalence. The D-ECCO working group along with other ECCO experts with expertise in nutrition, microbiology, physiology, and medicine reviewed the evidence investigating the role of diet and nutritional therapy in the onset, perpetuation, and management of IBD. A narrative topical review is presented where evidence pertinent to the topic is summarised collectively under three main thematic domains: i] the role of diet as an environmental factor in IBD aetiology; ii] the role of diet as induction and maintenance therapy in IBD; and iii] assessment of nutritional status and supportive nutritional therapy in IBD. A summary of research gaps for each of these thematic domains is proposed, which is anticipated to be agenda-setting for future research in the area of diet and nutrition in IBD.

Over the past years, mucosal healing has emerged as a major therapeutic goal in clinical trials in inflammatory bowel diseases. Accumulating evidence indicates that mucosal healing may change the natural course of the disease by decreasing the need for surgery and reducing hospitalization rates in both ulcerative colitis and Crohn's disease. Mucosal healing may also prevent the development of long-term disease complications, such as bowel damage in Crohn's disease and colorectal cancer in ulcerative colitis. Histologic healing may be the ultimate therapeutic goal in ulcerative colitis, whereas its impact on the course of Crohn's disease is unknown. Complete mucosal healing may be required before considering drug withdrawal. Targeting early Crohn's disease is more effective than approaches aimed at healing mucosa in longstanding disease. Several questions remain to be answered: should mucosal healing be systematically used in clinical practice? Should we optimize therapies to achieve mucosal healing? What is the degree of intestinal healing that is required to change the disease course? Large prospective studies addressing these issues are needed.

The healing of the intestine is becoming an important objective in the management of inflammatory bowel diseases. It is associated with improved disease outcome. Therefore the assessment of this healing both in clinical studies and routine practice is a key issue. Endoscopy for the colon and terminal ileum and computerized tomography or magnetic resonance imaging for the small bowel are the most direct ways to evaluate intestinal healing. However, there are many unsolved questions about the definition and the precise assessment of intestinal healing using these endoscopic and imaging techniques. Furthermore, these are relatively invasive and expensive procedures that may be inadequate for regular patients' monitoring. Therefore, biomarkers such as C-reactive protein and fecal calprotectin have been proposed as surrogate markers for intestinal healing. Nevertheless, the sensitivity and specificity of these markers for the prediction of healing may be insufficient for routine practice. New stool, blood or intestinal biomarkers are currently studied and may improve our ability to monitor intestinal healing in the future.

The second scientific workshop of the European Crohn's and Colitis Organization (ECCO) focused on the relevance of intestinal healing for the disease course of inflammatory bowel disease (IBD). The objective was to better understand basic mechanisms, markers for disease prediction, detection and monitoring of intestinal healing, impact of intestinal healing on the disease course of IBD as well as therapeutic strategies. The results of this workshop are presented in four separate manuscripts. This section describes basic mechanisms of intestinal healing, identifies open questions in the field and provides a framework for future studies.

Evidence supporting the importance of assessment of mucosal healing in inflammatory bowel disease has increased in the last years. Mucosal healing has been integrated in the assessment of treatment efficacy in ulcerative colitis, but in Crohn's disease this thought has arised after biological agents have been evaluated in clinical trials. Although a validated definition of mucosal healing still does not exist, its use is also assuming an increasingly important role in the follow-up of individual patients in clinical practice. Corticosteroids induce mucosal healing in a small proportion of patients with Crohn's disease and are of no benefit to maintain it. By contrast, mucosal healing in Crohn's disease can be achieved and maintained, with varying degrees of evidence and success, with thiopurines and biological agents. In ulcerative colitis, the ability of corticosteroids to induce mucosal healing is well recognized. 5-aminosalicylates, thiopurines and biological agents are also able to induce mucosal healing and, additionally, to maintain it. Mucosal healing assessment should be considered in clinical practice when symptoms persist despite therapy or when treatment discontinuation is being considered. Conversely, in patients whose clinical remission is not associated with mucosal healing, intensification of treatment is not currently recommended because of lack of evidence.

The fourth scientific workshop of the European Crohn's and Colitis Organization (ECCO) focused on intestinal fibrosis in inflammatory bowel disease (IBD). The objective was to better understand basic mechanisms and markers of intestinal fibrosis as well as to suggest new therapeutic targets to prevent or treat fibrosis. The results of this workshop are presented in three separate manuscripts. This section describes markers of fibrosis in IBD, identifies unanswered questions in the field and provides a framework for future studies addressing the unmet needs in the field of intestinal fibrosis.

The fourth scientific workshop of the European Crohn's and Colitis Organization (ECCO) focused on the relevance of intestinal fibrosis in the disease course of inflammatory bowel disease (IBD). The objective was to better understand the pathophysiological mechanisms of intestinal fibrosis, to identify useful markers and imaging modalities of fibrosis in order to assess its presence and progression, and, finally, to point out possible approaches for the prevention and the treatment of fibrosis.

The results of this workshop are presented in three separate manuscripts. This first section describes the most important mechanisms that contribute to the initiation and progression of intestinal fibrosis in IBD including the cellular and molecular mediators, the extracellular matrix molecules and matrix metalloproteinases/tissue inhibitors of metalloproteinases-system, the microbiota products, the role of fat, genetic and epigenetic factors, as well as the currently available experimental models. Furthermore, it identifies unanswered questions in the field of intestinal fibrosis and provides a framework for future research.

The fifth scientific workshop of the European Crohn’s and Colitis Organization (ECCO) focused on the relevance of fistulas to the disease course of patients with Crohn’s disease (CD). The objectives were to reach a better understanding of the pathophysiological mechanisms underlying the formation of CD fistulas; to identify future topics in fistula research that could provide insights into pathogenesis; to develop novel therapeutic approaches; and to review current therapeutic strategies (with clarification of existing approaches to prevention, diagnosis and treatment). The results of the workshop are presented in two separate manuscripts. This manuscript describes current state-of-the-art knowledge about fistula pathogenesis, including the roles of epithelial-to-mesenchymal transition and cytokine matrix remodelling enzymes, and highlights the common association between fistulas and stenosis in CD. The review also considers the possible roles that genetic predisposition and intestinal microbiota play in fistula development. Finally, it proposes future directions and needs for fistula research that might substantially increase our understanding of this complex condition and help unravel novel therapeutic strategies and specific targets for treatment. Overall, it aims to highlight unanswered questions in fistula research and to provide a framework for future research work.

Background and Aims: Perianal fistulas affect up to one-third of Crohn’s patients during the course of their disease. Despite the considerable disease burden, current treatment options remain unsatisfactory. The Fifth Scientific Workshop [SWS5] of the European Crohn’s and Colitis Organisation [ECCO] focused on the pathophysiology and clinical impact of fistulas in the disease course of patients with Crohn’s disease [CD].

Methods: The ECCO SWS5 Working Group on clinical aspects of perianal fistulising Crohn’s disease [pCD] consisted of 13 participants, gastroenterologists, colorectal surgeons, and a histopathologist, with expertise in the field of inflammatory bowel diseases. A systematic review of literature was performed.

Results: Four main areas of interest were identified: natural history of pCD, morphological description of fistula tracts, outcome measures [including clinical and patient-reported outcome measures, as well as magnetic resonance imaging] and randomised controlled trials on pCD.

Conclusions:The treatment of perianal fistulising Crohn’s disease remains a multidisciplinary challenge. To optimise management, a reliable classification and proper trial endpoints are needed. This could lead to standardised diagnosis, treatment, and follow-up of Crohn’s perianal fistulas and the execution of well-designed trials that provide clear answers. The prevalence and the natural history of pCD need further evaluation.

Data from Phase 3 studies in Crohn’s disease (CD) demonstrated significant improvements in endoscopic outcomes with risankizumab (RZB) versus placebo (PBO) following 12-weeks (wks) induction therapy. Continued maintenance therapy with 360mg RZB SC led to significantly higher rates of endoscopic response and remission at Wk52 compared to withdrawal/placebo. This post-hoc analysis examined the durability of SC RZB maintenance therapy for endoscopic outcomes among patients achieving these endpoints at the end of induction

Patients achieving clinical response with 12-wks IV RZB induction therapy in ADVANCE or MOTIVATE entered the maintenance study, FORTIFY, and received either RZB SC or had RZB withdrawn and received placebo for 52 wks. Forthis analysis, endoscopic outcomes in the RZB 360 mg SC (N=141) and withdrawal/placebo (N=164) arms are reported. Maintenance of endoscopic response, endoscopic remission, and/or an SES-CD score of 0-2 were assessed at Wk52 in patients who achieved these endpoints at Wk0 of maintenance (Wk12 of induction). Safety was assessed throughout the study.

Following 12-wks of IV RZB induction therapy (FORTIFY Wk0), 141 patients were randomized to RZB 360 mg (patients achieving endoscopic response, 55/141; endoscopic remission, 39/141; SES-CD score of 0-2, 29/141) and 164 were randomized to withdrawal (PBO SC) (patients achieving endoscopic response, 73/164; endoscopic remission, 46/164; SES-CD 0-2, 32/164). Maintenance of endoscopic response at Wk52 was demonstrated in 70.2% (39/55) of patients receiving RZB 360 mg SC versus 38.4% (28/73) of patients in the withdrawal (PBO SC) arm (P<0.001).  Maintenance of endoscopic remission at Wk52 was demonstrated in 74.4% (29/39) of patients receiving RZB 360 mg versus 23.9% (11/46) of patients in the withdrawal (PBO SC) arm (P<0.001).  Maintenance of an SES-CD score from 0-2 at Wk52 was demonstrated in  65.5% (19/29) of patients receiving RZB 360 mg versus 21.9% (7/32) of patients in the withdrawal (PBO SC) arm (P<0.001).RZB maintenance treatment was well-tolerated and no new safety signals were observed. The safety profile of RZB has been reported previously.^1–5

RZB IV induction followed by SC maintenance therapy led to sustained improvements in endoscopic outcomes, demonstrating the durability of efficacy with continued RZB treatment in patients with moderate to severe CD.  

References:
1 Feagan, B. G. et al.Lancet 389, 1699–1709 (2017) 2 Feagan, B. G. et al.Lancet Gastroenterol Hepatol 3, 671–680 (2018) 3 Ferrante, M. et al.Journal of Crohn’s and Colitis jjab093 (2021) 4 Ferrante, M. et al. in UEGW 2021 5 D’Haens, G. et al. in DDW 2021  

We used the postoperative recurrence model to better understand the role of AIEC bacteria in Crohn’s disease (CD), taking advantage of a well-characterized postoperative cohort.

From the REMIND prospective, multicenter cohort of operated CD patients (ileocolonic resection), AIEC identification was performed within the surgical specimen (M0) (N=181 patients) and the neo-terminal ileum (n=119 patients/181) during colonoscopy performed 6 months after surgery (M6). Endoscopic postoperative recurrence was graded using Rutgeerts’ index, which was interpreted, either from a clinical point of view (postoperative endoscopic recurrence ≥ i2b or severe ≥ i3), or from a pathophysiological point of view (reappearance of the first ileal lesions = i1 and more advanced postoperative ileal recurrence = i2b + i3). The mucosa-associated microbiota was analyzed by 16S sequencing at M0 and M6. Relative risks (RR) or odds ratios (OR) were adjusted on potential confounders ((gender, smoking, CD duration, CD phenotype, prior bowel resection, indication for surgery, granuloma, preventive treatment, antibiotics).

Among the 228 patients included at the time of the analyzes, the search for AIEC was carried out in 181 patients at M0, and 119 patients at M6. Among these 181 patients included in our study, 46.3% did not receive any preventive treatment for endoscopic postoperative endoscopic recurrence while 24.3% have been treated with anti-TNF to prevent postoperative recurrence.

AIEC prevalence was two-fold higher within the neo-terminal ileum at M6 (30.3%) than within the surgical specimen (14.9%) (p<0.001). AIEC within the neo-terminal ileum at M6 was associated with higher rate of early ileal lesions (i1) (41.6% vs 17.1%; aRR=3.49[1.01-12.04], p=0.048) or ileal lesions (i2b + i3) (38.2% vs 17.1%; aRR=3.45[1.06-11.30], p=0.040) compared to no lesion (i0). AIEC within the surgical specimen was predictive of higher risk of i2b-endoscopic POR (aOR=2.54[1.01-6.44], p=0.049) and severe endoscopic POR (aOR=3.36 [1.25-9.06], p=0.017). While only 5.0% (6/119) of the patients were AIEC-positive at both M0 and M6, 43.7% (52/119), patients with history of AIEC infection (M0 or M6) had higher risk of ileal endoscopic POR (aOR=2.32 [1.01-5.39], p=0.048]), i2b-endoscopic postoperative recurrence (aOR = 2.41[1.01-5.74]; p=0.048) and severe endoscopic postoperative (aOR = 3.84[1.32-11.18], p=0.013). AIEC colonization was associated with a specific microbiota signature including increased abundance of Ruminococcus gnavus.

Based on the postoperative recurrence model, our data support the role of AIEC in the early steps of ileal CD.