Subcutaneous (SC) formulations of CT-P13 and vedolizumab (VED) are currently available as new treatment option for patients with inflammatory bowel disease (IBD). The decision to switch requires a shared decision making based on adequate education of the patient, to avoid negative outcomes due to a nocebo effect. The aims of this study were (1) to evaluate the percentage of patients with IBD in favour of switching to SC formulations and (2) to compare two educational strategies.

This was a multicentre study in patients with IBD on maintenance intravenous (IV) CT-P13 or VED. Patients attending the infusion unit were invited to complete a survey exploring the willingness to switch to SC formulations. In centre A, all patients were informed on the new SC formulations and the accompanying care pathway by an information leaflet and a face-to-face interaction with the IBD nurse, prior to completing the survey. In centre B, patients on a minimal interval of q8w were digital invited to the same survey via the e-health application of the hospital. Demographics, patient reported outcomes, willingness to switch and reasons for IV vs. SC preferences were captured.

In total, 447 (n=183 Centre A; n=264 Centre B; participation ratio 83.6%) patients completed the survey (m/f: 212/235; CD/UC/IBD-U: 275/161/11; median age 45 IQR 33-57; remission CD/UC: 75%/82%) see table. Most patients were open to SC treatment (47% yes, 33% doubt, 20% no). The main driver to switch was an anticipated decrease in hospital visits (86%) and overall time gain (78%). The main reason to continue IV was fear of change (60%) and uncertainty in case of relapse after switch to a SC formulation (46%). In univariate analysis, the self-estimated compliance rate was associated with the willingness to switch (p<0.0001). To evaluate the impact of the approach in patient education between the two centres, we compared the subgroup of patients on ≥q8w interval with a dosing of 5-10mg/kg CT-P13 or 300 mg VED (n=335). The willingness to switch was higher after a face-to-face approach (centre A) compared to a merely digital approach (centre B;  53.9 % vs. 40.9 % p=0.038), although patients in centre B had a higher educational level (p=0.003), more prior experience with other IBD SC medication (p=<0.001), lived further from the hospital (p<0.001) and had a younger age at diagnosis (p=0.019).

In this multicentre comparative study exploring the willingness to switch from IV to SC maintenance therapy with CT-P13 and VED, the majority is open to switch to a SC formulation. The direct approach and education of the patient by the IBD nurse impacts significantly the willingness to switch. In a follow-up we will investigate the actual switch rates.

1. To review flare management and optimisation of biologic treatments using TDM  
2. To choose an appropriate therapy for pregnant IBD patients
3. To learn how to plan peri-partum care

1. To review the therapeutic goals and patient needs in UC
2. To confer different treatment strategies in UC
3. To discuss therapeutic options in UC
4. To emphasize the advantage of tight disease control

We sought out to identify proteomic markers of anti-Tumor Necrosis Factor (TNF) treatment failure in anti-TNF naive patients with Crohn's disease, using data obtained from the Personalised Anti-TNF Therapy in Crohn's disease (PANTS) study.

Background

The first line treatment for inducing remission in pediatric Crohn’s disease (CD) is Exclusive Enteral Nutrition (EEN), where a patient drinks a nutritionally complete formula exclusively for 6 to 12 weeks. Despite the effectiveness of EEN, some patients may experience challenges including taste fatigue, monotony, and a lack of social participation with meals. Given these challenges, patients may turn to popular or fad diets for managing their disease. These diets are often restrictive, eliminating a number of foods and exacerbating the risk of underlying nutrient deficiencies in this patient population.

Methods

These case studies involved a nutrient analysis of evidence-based and popular diets for CD, including Crohn’s Disease Exclusion Diet (CDED), CD-TREAT, Specific Carbohydrate Diet (SCD), IBD Anti-inflammatory Diet (IBD-AID), Autoimmune Protocol (AIP) Diet, Gut and Psychology Syndrome (GAPS) Diet, and low FODMAP. Four cases were selected with mild-moderate CD: 11-year-old and 16-year-old, both male and female. A nutrient analysis of sample menus of each diet was completed using Food Processor version of 11.6.0 by ESHA Research. Results were compared to age and gender specific Dietary Reference Intakes (DRIs), population-based dietary intake data, and Health Canada Dietary Guidelines.

Results

Data are presented for Case 1, 11-year-old male. Findings were comparable to other age and gender cases. As compared to Acceptable Macronutrient Distribution Ranges (AMDRs), there was a higher percentage of energy from fats and lower from carbohydrates for the SCD (% kcal, fat and carbohydrate respectively: 59%; 30%), IBD-AID (52%; 37%), AIP Diet (50%; 20%) and GAPS Diet (60%, 21%). Saturated fat intake exceeded recommendations (>10% of energy intake) for CDED (% kcal, 14%) CD Treat (17%), SCD (11%), AIP Diet (15%) and GAPS Diet (20%). Both vitamin D and/or calcium intake were below the Recommended Dietary Allowance (RDA) respectively for CDED (% RDA, vitamin D and calcium respectively: 89%; 86%), SCD (23%; 53%), AIP Diet (14%; 23%), low FODMAP Diet (4%, 96%) and GAPS Diet (calcium, 58%). Adolescent females versus males between the ages of 14-18 years may be at greater risk of inadequate nutrient intake, given the general increase in nutrient requirements yet lower caloric needs.

Conclusion

Given the increase in awareness and interest in popular diets for Crohn’s disease, it is imperative that clinicians are aware of the risks of inadequate nutrient intake with restrictive diets.

Upadacitinib (UPA), an oral, reversible, Janus kinase (JAK)-1 selective inhibitor can induce clinical and endoscopic remission after 8 weeks in patients (pts) with moderately to severely active Ulcerative Colitis (UC). To provide mechanistic insights into downstream effects of UPA in the intestinal mucosa, we evaluated pharmacodynamic modulation of gene expression in colon biopsies from pts with UC in the Phase 2b study, U-ACHIEVE (NCT02819635). These analyses aimed to link molecular changes to clinical endpoints. 

Transcriptomic data were collected from rectosigmoid biopsies at baseline (BL) and Week (Wk) 8 in a subset of pts in sub-study 1 of U-ACHIEVE (N=88: placebo [PBO], n=15; pooled UPA 15, 30 & 45 mg, n=73). Samples underwent bulk RNA sequencing and differentially expressed genes (DEG) (false discovery rate [FDR]<0.05 & |log fold change [FC]|>1) from BL to Wk 8 were identified with linear mixed-effect models. DEG were analysed with KEGG and GO pathway enrichment and clinical endpoint responder analysis. Cellular profiling with gut cell deconvolution based on defined cell types was undertaken.¹ 

At Wk 8, expression of 695 gut genes was modulated (FDR<0.05 & |logFC|>1) from BL after UPA treatment compared with no DEG in PBO pts (including responders). Of these genes, ~70% (n=492) were downregulated and enriched in inflammatory pathways including T- and B-cell effector responses, neutrophil-mediated immunity, and leukocyte chemotaxis. Also, irrespective of directionality, most DEG from BL to Wk 8 in UPA-treated pts were associated with clinical response and remission, and histologic and endoscopic improvement. At Wk 8, deconvoluted cell fractions associated with adaptive but also innate inflammatory cells in the gut of UPA responders were decreased compared with non-responders; in contrast, fractions associated with enterocyte, secretory goblet cell and myofibroblast cells were increased in responder gut tissue (Fig 1). Modulation of genes associated with UC disease activity (OSM & S100A8/9 [calprotectin]), Th1 (TBX21, IFNG), Th2 (GATA3, IL5RA, IL13RA2), Th9 (SPI1), Th17 (IL17A, IL23A, IL21R), B-cell responses (BTK, CD40), barrier function (ESPN, VIL1, CLDN23, OCLN, MUC1/2/12/16/20) and wound repair (ANXA1/6/13, MMP7/9) were associated with clinical improvement at Wk 8 (Fig 2).

JAK inhibition with UPA is associated with transcriptional changes in colonic mucosa that are seen with UC disease pathophysiology. Clinical benefit mediated by UPA is associated with modulation of molecular biomarkers of UC disease activity, T-helper-cell differentiation, B-cell-mediated responses, gut barrier function and wound healing.

1. Menden K, et al. Sci Adv 2020;6:eaba2619

Upadacitinib (UPA), an oral, reversible JAK inhibitor engineered for increased selectivity for JAK1 over JAK2, JAK3, or tyrosine kinase 2 (TYK2), demonstrated significantly greater efficacy compared with placebo (PBO) for induction of remission in patients with moderately to severely active ulcerative colitis (UC) in two phase 3 trials, U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026). This analysis evaluated the efficacy of UPA on early symptomatic improvement for the first 14 days, using pooled data from U-ACHIEVE Induction and U-ACCOMPLISH.

U-ACHIEVE and U-ACCOMPLISH were multicentre, double-blind, PBO-controlled trials that enrolled patients who have had moderately to severely UC with an Adapted Mayo Score of 5 to 9 points and centrally reviewed endoscopy subscore of 2 to 3. A total of 998 patients were randomized to receive UPA 45mg once daily (QD) (n=658) or PBO (n=328) for 8 weeks (wks) in a 2:1 ratio. First dose of study drug was administered on Day 0. Improvement in symptoms including stool frequency subscore (SFS), rectal bleeding subscore (RBS), abdominal pain, and bowel urgency were analysed from daily symptom diary data. Multivariate regression analysis was used to determine if early changes in UC symptoms could be used to evaluate a potential correlation with patients’ likelihood of achieving clinical response or clinical remission per Adapted Mayo score at the end of induction.

Baseline characteristics were similar between both treatment groups. Patients treated with UPA 45 mg QD experienced significant improvement in daily symptoms, with significantly more subjects achieving SFS≤1 (p<0.001), RBS of 0 (p<0.05), and SFS of 0 (p<0.05) as early as day 1 and maintained through day 14 (Figure 1). A significantly higher percentage of patients who received UPA 45 mg QD compared to PBO, achieved abdominal pain=0 and the absence of bowel urgency within 3 days of beginning treatment through day 14 (p<0.05). Multivariate analysis revealed that patients who achieved day 7 SFS≤1 (OR 2.42, 95% CI, 1.53-3.82) were more likely to attain clinical response (Table). Patients who attained day 7 SFS≤1 (OR 2.53, 95% CI 1.59-4.00) or day 7 bowel urgency absent (OR 2.40, 95% CI 1.52-3.79) were more likely to achieve clinical remission at week 8.

UPA 45 mg QD significantly improved UC symptoms as early as day 1, providing patients with rapid symptom relief. Patients who achieved early symptom improvement were more likely to attain clinical remission or clinical response at week 8. [Clinicaltrials.gov, U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026)]

Inflammatory bowel disease (IBD) increases colorectal cancer risk. To mitigate this patients undergo endoscopic surveillance to detect dysplasia. However, chronic inflammation alters mucosal and vascular colonic architecture, complicating lesion recognition. Endoscopic advances enhance our ability to accurately characterise these lesions. But training on optical diagnosis of dysplastic lesions in IBD is not widely available. We aim to fill this gap by developing and validating the new OPTIC-IBD online training platform (Figure 1, NCT04924543, funding GutsUK TRN2019-03).

We designed an interactive, self-directed, multi-modality learning module. This includes surveillance principles, optical diagnosis methods, characterisation approach, classifications (SCENIC, Kudo, FACILE¹), examples and self-assessments. We invited participants from Canada, Italy and the UK, including novice (<100 lifetime colonoscopies), intermediate and experienced endoscopists (≥1000). Assessments comprised 24 short endoscopic videos of IBD colonic lesions, divided into 8 non-dysplastic (hyperplastic, inflammatory, sessile serrated lesion [SSL]) and 16 dysplastic lesions (SSL-D, low grade and high grade dysplasia, cancer). Participants classified lesions, predicted histology and rated their confidence. All participants completed online training and feedback. The videos were repeated in a random order after ≥7 days. Participants were then randomised 1:1 to get feedback and extra training. All had a final assessment at 60 days with prior/new videos and similar case mix. We report diagnostic performance for dysplasia, interrater reliability and rater confidence.

We present a planned interim analysis of 77 participants after pre- and post-course assessments (Table 1). Diagnostic accuracy improved (primary endpoint: 44.5 to 54.0%, P<0.0001), particularly for novice and intermediate endoscopists. Sensitivity for dysplasia increased (50.3 to 59.1%) in line with prior experience. Specificity and accuracy were most improved for high confidence diagnoses (44.9 to 70.3% and 55.0 to 64.6%). In multilevel logistic regression, training was associated with correct diagnoses for high confidence (OR 1.40, 1.13-1.77) but not low confidence ratings (OR 1.09, 0.96-1.25). Training improved precision between participants (Table 2) and their confidence (Table 3).

The OPTIC-IBD training module improved participants’ accuracy, precision and confidence in optical diagnosis of dysplasia. Next, we will study the training approaches and classification systems that can best be adopted by non-experts and trainees. Our refined training platform will be made available to improve quality of endoscopic care for people with IBD.

1. Iacucci et al Endoscopy 2019;51(2):133

Vasculitis are a group of rare and potentially life-threatening diseases which are usually classified by the size of the vessels predominantly affected. 
Vasculitis may rarely co-exist with IBD (both UC and CD) as an extra-intestinal manifestation or in association.
There are few small case series and literature reviews in the literature on vasculitis in IBD.

Learning Objectives:
- Definition of vasculitis and how are they classified
- Association between IBD and vasculitis
- Which types are more associated with CD and UC
- Histological features of vasculitis

Pouchitis is a common complication of ileal pouch-anal anastomosis (IPAA) after proctocolectomy in ulcerative colitis (UC). There are currently no approved therapies for chronic pouchitis. Here, we report a multicentre trial of intravenous (IV) vedolizumab (VDZ) for chronic pouchitis after IPAA in patients with UC.

EARNEST was a randomised, double-blind, placebo (PBO)-controlled, phase 4 study of VDZ in patients aged 18-80 years with chronic pouchitis after proctocolectomy with IPAA for UC (NCT02790138). Male and female patients with a history of IPAA for UC and chronic pouchitis were eligible. Patients were randomised (1:1) to receive VDZ IV (300 mg) or PBO on Day 1 and at Weeks (W) 2, 6, 14, 22 and 30, as well as ciprofloxacin for the first 4 weeks. The primary endpoint was modified Pouchitis Disease Activity Index (mPDAI) remission at W14; efficacy was also assessed through other mPDAI/PDAI secondary endpoints and endoscopic exploratory endpoints (assessed by a central reviewer) at W14 and W34. Safety (adverse events [AEs]) was monitored throughout the study.

In total, 102 patients were treated (51 per group). Patients had a mean age of 40.8 years (VDZ) and 42.9 years (PBO). mPDAI remission rates (comprising clinical symptoms and endoscopy domains) were 31.4% (n=16/51) for VDZ vs 9.8% (n=5/51) for PBO at W14 (p=0.013; Figure 1). Significant differences in favour of VDZ over PBO were also seen in mPDAI remission at W34, mPDAI response at W14 and W34, and PDAI remission (comprising clinical symptoms, endoscopy and histology domains) at W14 and W34 (Figure 1). The rate of sustained remission (defined as remission at both W14 and W34) was higher for VDZ vs PBO on both the mPDAI (VDZ 27.5% [n=14/51] vs PBO 5.9% [n=3/51]; difference 21.6 percentage points [95% confidence interval (CI), 6.5-37.0]) and the PDAI (VDZ 31.4% [n=16/51] vs PBO 7.8% [4/51]; difference 23.5 percentage points [95% CI, 8.0-38.8]). Endoscopic ulceration analysis showed greater reductions in number of ulcers from baseline for VDZ over PBO at W14 and W34 (Figure 2). A higher proportion of patients in the VDZ vs PBO group had an improved SES-CD score and achieved SES-CD remission of pouchitis (Figure 2). AE rates were similar between groups and no new safety signals were identified (Table).

This is the first and largest randomised, double-blind PBO-controlled trial of biologic therapy to show significant benefits across multiple treatment outcomes in patients with chronic pouchitis after IPAA for UC. VDZ showed consistent treatment benefits over PBO across clinical, endoscopic and histologic endpoints, together with safety consistent with its established profile.

Patients admitted to hospital with active Inflammatory bowel disease(IBD) are at increased risk of thromboembolism. Surgical specialties have demonstrated benefits of thromboembolism prophylaxis after hospital discharge in high risk groups.

This study aims to identify IBD patients at increased risk and develop a scoring system to recognise them.

Hospital episode statistics data was used to identify all patients admitted for IBD emergently or electively for surgery. All Patients with a thromboembolism within 90 days of hospital discharge were identified. A multilevel logistic regression model was used to identify patient and admission level factors associated with increased risk of thromboembolism. A scoring system to identify higher risk patients was constructed based on this model. Score performance was assessed using bootstrapped data.

201,779 admissions in 101,966 patients were included. The rate of thromboembolism within 90 days was 17.24 per 1000 patient years at risk. This was highest in patients admitted as an emergency undergoing surgery (36.91) followed by emergency admission without surgery (15.63) and elective admission for surgery (15.60). The rate of thromboembolism between 180 and 270 days following discharge was 0.84, 1.59 and 1.70 per 1000 patient years at risk respectively.

Regression analysis demonstrated that female gender (OR 0.65(95%CI 0.53-0.80),p<0.001), increasing age (49-60 years,(4.73(3.40-6.58),p<0.001), increasing length of stay; 5-7 days (1.77(1.27-2.46),p=0.001), 7-10 days (1.91(1.40-2.60),p<0.001), >10 days (4.04(2.98-5.46),p<0.001), increasing number of prior admissions for IBD in preceding 3 months; 1 (1.36(1.11-1.68),p=0.004), 2 (1.66(1.23-2.22),p=0.001), >2 (2.32(1.67-3.21),p<0.001), Ulcerative Colitis (1.46(1.19-1.79),p<0.001) and admission type compared to Elective surgery (Emergency admission including surgery (1.64(1.15-2.33),p=0.006)), (Emergency admission not including surgery(1.57(1.07-2.32), p=0.023)) were statistically significant associations.

In the scoring system, a score >=9 gave a positive predictive value of 1%. The AUC was 0.71(95%CI 0.69-0.72)

Patients admitted to hospital have ongoing increased risk of thromboembolism in the 90 day period following discharge. Risk was increased in patients with prolonged length of stay, increasing age, male gender or admitted as an emergency requiring surgery. Higher risk patients were identifiable by a scoring system.

An overview of wearable and remote technology for monitoring of IBD

Objectives:
1. To link between changes in IBD incidence rates and changes in lifestyle habits around the world
2. To demonstrate the global association between ultra-processed food intake and IBD risk
3. To review the literature focusing on the Mediterranean diet and IBD across the globe

What is the optimal timing and methods for monitoring?

Educational objectives:
1. To understand the importance of disease monitoring in a treat-to-target strategy
2. To understand the difference between a treatment target and an instrument of tight disease control
3. To understand the need for a non invasive patient-friendly disease monitoring
4. To emphasize a proposal for a structured time-bound monitoring

 Disease monitoring is the corner-stone of a treat-to-target strategy. The definition of the treatment target is linked to our understanding of the disease process and the availability of markers to assess the disease process. Beside the target, we may define several steps to reach the target which are associated with specific tools and markers. Monitoring tools are not unique and must be articulated in a time-bound manner to allow an optimal disease control aiming at alleviating the symptoms and avoiding disease progression. In particular is a full endoscopic healing is currently the most widely accepted objective, intermediate steps may include symptomatic improvement and biomarkers improvement and normalization.

Up to 50% of Crohn’s patients develop intestinal strictures during their disease course. In general, predominant-inflammatory strictures are likely to benefit from anti-inflammatory medical therapy, whereas predominant-fibrotic strictures often require endoscopical/surgical approach. However, rarely is a stricture merely inflammatory or fibrotic; they are typically characterised by a mixture of inflammation, muscular hypertrophy, collagen disposition and fibrosis. Cross-sectional imaging techniques allow full-thickness evaluation of the bowel wall, of which IUS is non-invasive, cost-effective and can be used in the point-of-care setting, which makes is an attractive tool for monitoring.
The aim of the talk is to review the challenges of distinguishing inflammatory and non-inflammation strictures on conventional B-mode IUS and on advanced US modalities, such as CEUS and elastography.  

To understand imaging findigs of Fibrosis on cross sectional imaging with emphasis on MR-E 
To review litterature on MR-E and fibrosis
To have an overview over new imaging tools of Fibrosis (delayed enhancement, DWI, IVIM, Magnetization trasfert, Motility study).

Educational Objectives:
1. To appreciate the strong impact of the diet on gut microbial community structure and function
2. To understand the role of the diet in the pathogenesis of experimental gut inflammation
3. To review a role of the diet on the development and course of human inflammatory bowel diseases

1) Overview of the aetiology of IBD
2) Discussion of the impact of the environment on disease onset, course and response to therapy
3) Focus on the emerging evidence of a role of diet on disease onset from animal models, epidemiology and human studies
4) Discussion of the potential to modify the environment as a preventative strategy / therapy