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Tofacitinib for the treatment of Ulcerative Colitis: An integrated summary of safety data from the global OCTAVE and RIVETING clinical trialsECCO'22 Virtual
Year: 2022
Authors: Remo Panaccione
Background

Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Efficacy and safety of tofacitinib were evaluated in randomised, placebo-controlled Phase (P)2 (NCT00787202) and P3 (NCT01465763; NCT01458951; NCT01458574) studies, an open-label, long-term extension (OLE) study (NCT01470612) and an ongoing P3b/4 study (NCT03281304). We report updated tofacitinib safety analyses from the tofacitinib UC clinical programme, with inclusion of a 6‑month interim analysis of data from the P3b/4 study, up to 7.8 years of tofacitinib exposure.

Methods

This analysis included1157 patients (pts) receiving tofacitinib 5 or 10 mg BID from completed P2/P3/OLE studies, and the ongoing P3b/4 study (as of 20 Feb 2020; Overall+P3b/4 Cohort). Proportions and incidence rates (IRs; unique pts with events/100 pt‑years [PY] of exposure) were evaluated for deaths and adverse events (AEs) of special interest. Opportunistic infections (OIs), malignancies, major adverse cardiovascular events (MACE) and gastrointestinal perforations were adjudicated.

Results

Table 1 shows demographics and clinical characteristics. In the Overall+P3b/4 Cohort, 1157 pts received ≥1 dose of tofacitinib 5 or 10 mg BID; 955 (83%) received a predominant dose of 10 mg BID; 397/1157 (34.3%) pts had received tofacitinib for >4.1 years. Median treatment duration was 623 (range, 1–2850) days (2999.7 PY of exposure). Table 2 shows safety data for AEs of special interest in the Overall+P3b/4 Cohort. IRs (95% confidence intervals) for all tofacitinib doses: deaths, 0.23 (0.09, 0.46); serious infections, 1.69 (1.26, 2.21); herpes zoster (non-serious and serious), 3.30 (2.67, 4.04); OIs, 1.03 (0.70, 1.46); malignancies (excluding non-melanoma skin cancer [NMSC]), 0.84 (0.55, 1.24); NMSC, 0.73 (0.45, 1.10); MACE, 0.29 (0.13, 0.55); deep vein thrombosis, 0.03 (0.00, 0.18); pulmonary embolism, 0.19 (0.07, 0.42); and gastrointestinal perforations, 0.10 (0.02, 0.28). IRs for AEs of special interest were similar to prior Overall Cohort analyses.1

Conclusion

The safety profile of tofacitinib in pts with UC from the tofacitinib UC clinical programme was generally consistent with that of other UC therapies, including biologics, with the exception of herpes zoster.2 IRs for AEs of special interest have remained stable over an extended period of time (up to 7.8 years) with inclusion of final data from the OLE study and an interim analysis of data from the P3b/4 study.1,3

References:
1. Sandborn WJ et al. United European Gastroenterol J 2021; 9 (Suppl 8): Abstract OP152.
2. Curtis JR et al. Inflamm Bowel Dis 2021; 27: 1394-1408.
3. Sandborn WJ et al. United European Gastroenterol J 2020; 8 (Suppl 8): Abstract OP494.


Tough and little – dealing with VEOIBD9th P-ECCO Educational Course - Paediatric IBD: When the going gets tough
Year: 2022
Authors: Lissy de Ridder
Summary content

Paediatric Inflammatory Bowel Disease (IBD) accounts for 10-15% of all incident cases, while incidence in children under 10 years old is rising most rapidly. Very early-onset inflammatory bowel disease (VEOIBD) is diagnosed before the age of 6 years while infantile IBD occurs before the age of 2 years and may be a clue for monogenic IBD..

It is very important to identify monogenic IBD patients as management may differ from classical IBD. While age of onset is most relevant, specific comorbidity and extraintestinal manifestations also are of particular relevance in identification of monogenic IBD. These conditions are summarized in the following: Young agematters most. Young age onset; Multiple family members and consanguinity; Autoimmunity; Thriving failure; Treatment with conventional medication fails; Endocrine concerns; Recurrent infections or unexplained fever; Severe perianal disease; Macrophage activation syndrome and HLH; Obstruction and atresia of intestine; Skin lesions, dental and hair abnormalities; Tumours. This anagram will be further elucidated.

A diagnostic algorithm of monogenic IBD will be discussed, incorporating multidisciplinary team assessment of genetic results, genetic counselling but also the need for functional assessment of novel gene defects and variants of unknown significance to establish causality. Also, illustrative cases of monogenic IBD such as Interleukin-10 receptor deficiency and XIAP will be incorporated in the presentation.

Tough biological choices in PIBD: What to choose, when to move, and can we combine?9th P-ECCO Educational Course - Paediatric IBD: When the going gets tough
Year: 2022
Authors: Anne Griffiths
Transcriptional signatures of blood derived immune cells associated with disease location-based heterogeneity in IBDECCO'22 Virtual
Year: 2022
Authors: Padhmanand Sudhakar
Background

Disease location is a prominent axis of heterogeneity in Inflammatory Bowel Disease (IBD) with many implications. Using genome-wide profiling of the transcriptome of monocytes and CD4+ T cells isolated and purified from whole blood, we aimed to identify molecular signatures and mechanisms associated with different locations among IBD patients.

Methods

Blood was collected from 125 IBD patients (87 CD, 38 UC) with endoscopy-proven active disease (presence of ulcerations). Cell separation and fluorescence activated cell sorting were performed to separate the monocyte and CD4+ T cell fractions, from which RNA was subsequently isolated and sequenced (Illumina HiSeq 4000NGS). We used different supervised and unsupervised approaches (differential expression, pathway based data integration, latent factor based models, regularized generalized canonical correlation analysis and co-expression networks) to interpret the differences in the gene expression datasets of monocytes and CD4+ T cells from patients with different disease locations (Montreal classification). Functional enrichment analysis was performed using the ReactomePA package. Regulatory relationships and therapeutic relevance information were retrieved from the ChEA3 and the OpenTargets resources respectively. Comparison with single-cell and bulk-derived gene expression signatures from other auto-immune diseases were performed using the ADEX resource.

Results

Highly variant disease-location (DL)-associated genes (FDR <= 0.1) in monocytes and CD4+ T cells were identified using latent factor based unsupervised models. These genes were known to be involved in IBD pathogenesis and/or intestinal inflammation.  Additional supervised analysis revealed significant differences in CD4+ T cells between ileal CD patients and UC patients.  RAF-independent MAPK-activation pathway and FOXO-mediated transcriptional pathway (downregulated in UC patients) were over-represented (FDR <= 0.05) among the features distinguishing ileal CD and UC patients based on signature sets derived from the above-mentioned multiple approaches.  Of note was the finding that 12.5% of the DL associated co-expression modules were also annotated as IBD drug targets. Based on gene expression signature from bulk and single-cell sources, the DL associated genes were found to be active in many other auto-immune diseases such as rheumatoid arthritis, systemic sclerosis, Sjögren’s syndrome, type 1 diabetes and Systemic lupus erythematosus, suggesting their role in mediating immune malfunctions.

Conclusion

We identified signaling pathways and transcription factors which could drive the expression differences observed in the circulating immune cells between ileal CD and UC patients. 

Transmural vs. endoscopic healing in CD: What is the ultimate goal? (Tandem talk)ECCO'22 Virtual
Year: 2022
Authors: Torsten Kucharzik; Christian Maaser
Summary content

Educational objectives

How to define endoscopic remission (ER) and transmural remission (TR) in Crohn’s disease

PROS and CONS for endoscopic remission in CD

PROS and CONS for transmural remission in CD

Potential algorithm on how and when to assess ER and TR as potential treatment target in CD


Type of patient education impacts the willingness to switch from an IV to SC of a biological in patients with Inflammatory Bowel Disease: a multicentre, comparative study.16th N-ECCO Network Meeting
Year: 2022
Authors: Els De Dycker
Background

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.

Methods

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.

Results

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).

Conclusion

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.

table demographics

UC cases presentation A) Newly diagnosed UC B) Persistent active UC C) Panel discussion - Q&A and conclusion2nd ECCO Postgraduate Course in IBD
Year: 2022
Authors: Sophie Restellini; Pascal Juillerat; Glen Doherty; Britta Siegmund
Summary content

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

UC Management13th N-ECCO School
Year: 2022
Authors: Mark Samaan
Summary content

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

Understanding the mechanisms of anti-TNF treatment failure in patients with Crohn’s Disease: A proteomic analysis of the PANTS cohort8th Y-ECCO Basic Science Workshop
Year: 2022
Authors: Neil Chanchlani
Summary content

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.

Unpacking the different popular diets for pediatric Crohn's Disease - concerns around nutritional adequacy7th D-ECCO Workshop
Year: 2022
Authors: Erin Carmody

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 modulates inflammatory pathways in gut tissue in patients with Ulcerative Colitis: Transcriptomic profiling from the Phase 2b study, U-ACHIEVEECCO'22 Virtual
Year: 2022
Authors: Bram Verstockt
Background

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. 

Methods

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.

Results

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).

Figure 1



Figure 2

Conclusion

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 Therapy Reduces Ulcerative Colitis Symptoms as Early as Day 1ECCO'22 Virtual
Year: 2022
Authors: Séverine Vermeire
Background

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.

Methods

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.

Results

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.

Conclusion

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)]

Validation of a new OPtical diagnosis Training platform to Improve dysplasia Characterisation in Inflammatory Bowel Disease (OPTIC-IBD): A multicentre randomised controlled studyECCO'22 Virtual
Year: 2022
Authors: Richard James Michael Ingram
Background

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).

OPTIC-IBD study designMethods

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.

Results

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).
Table 1
Table 2
Table 3

Conclusion

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 in/ related to IBD7th H-ECCO IBD Masterclass
Year: 2022
Authors: Francesca Rosini
Summary content

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

Vedolizumab intravenous is effective across multiple treatment targets in chronic pouchitis: Results of the randomised, double-blind, placebo-controlled EARNEST trialECCO'22 Virtual
Year: 2022
Authors: Simon Travis
Background

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.

Methods

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.

Results

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).





Conclusion

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.

Venous thromboembolism following discharge from hospital in patients admitted for Inflammatory Bowel DiseaseECCO'22 Virtual
Year: 2022
Authors: Philip Harvey
Background

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.

Methods

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.

Results

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)

Conclusion

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.

Wearable devices in IBD - Is this the future?8th ClinCom Workshop
Year: 2022
Authors: Uri Kopylov
Summary content

An overview of wearable and remote technology for monitoring of IBD

What can we learn about the role of diet in IBD from across the globe?7th D-ECCO Workshop
Year: 2022
Authors: Lihi Godny
Summary content

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 can we learn from rheumathology in terms of sequencing therapies (Tandem talk)ECCO'22 Virtual
Year: 2022
Authors: Daniel Aletaha; Maria Antonietta D'Agostino
What environmental factors are modifiable? Lessons from non-IBD conditionsECCO'22 Virtual
Year: 2022
Authors: Benoit Nemery de Bellevaux