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Pyroptosis Inhibition Prevents the Cytotoxicity Induced by IL-17 Without Impairing Its Beneficial EffectsECCO'22 Virtual
Year: 2022
Authors: Sung Noh Hong
Background

Th17 cells and their main secreting cytokine interleukin-17A (IL-17) are considered as the main pathogenic factors in inflammatory bowel diseases (IBDs). However, anti-IL-17 neutralizing antibodies, a theoretically curative medication for IBDs, paradoxically aggravated intestinal inflammation. The mechanisms by which it mediates the protective and pathologic effects of IL-17 remain unclear in the intestinal epithelium.

Methods

The intestinal epithelial responses induced by IL-17 was evaluated using the human small intestinal organoid (enteroid) model.

Results

Organoid-forming efficiency, cell viability and proliferation of enteroids were decreased in proportion to the concentration of IL-17, which did not differ between the enteroids derived from controls and patients with Crohn’s disease. Bulk RNA-sequencing revealed the enrichment of secretion signaling in IL17-treated enteroids. Among its components, PIGR was up-regulated significantly as the concentration of IL-17 increased, resulting in IgA transcytosis and protective role against pathogens. The IL-17-induced cytotoxicity was predominantly mediated by pyroptosis with activation of CASP1 and cleavage of GSDMD. Single-cell RNA- sequencing identified pyroptosis occurred actively in intestinal stem cells (ISCs) and enterocytes. Anti-IL-17 antibody, izekizumab, completely restored IL-17-induced cytotoxicity, but suppressed mucin secretion and IgA transcytosis. CASP1 inhibitor, Ac-YVAD-cmk, restores cytotoxicity induced by IL-17, without impairing its beneficial effects.

Conclusion

IL-17 induces pyroptosis of ISCs and enterocytes, as well as mucin secretion and PIGR-induced IgA transcytosis. Paradoxical gastrointestinal effects of IL-17 neutralizing antibodies may be associated with inhibition of mucin secretion and IgA transcytosis. The inhibition of pyroptosis using the CASP1 inhibitor prevents the cytotoxicity induced by IL-17 without compromising its beneficial effects.

Radiology in Crohn's Disease7th H-ECCO IBD Masterclass
Year: 2022
Authors: Julián Panés; Jordi Rimola
Summary content

Diagnosis and monitoring of Crohn’s disease (CD) incorporates laboratory parameters and both endoscopic and radiological assessments. Cross-sectional imaging (computed tomography and magnetic resonance enterography [CTE/MRE]), has shown high diagnostic accuracy for detecting small bowel and colonic CD, and provides complementary findings to ileocolonoscopy. Quantitative measurements wall thickness, contrast enhancement, T2 hyperintensity, and direct identification of ulcerative lesions have demonstrated correlation with ileoscopic and histological findings of inflammation. Wall thickening and on MRE correlate with histological findings of inflammation. Following medical treatment, radiological remission [or transmural normalization] by MRE or CTE parallels endoscopic healing with an estimated accuracy of 90%. Additional studies have also shown that the radiological response of inflamed bowel segments to medical therapy is associated with improved long-term outcomes, including reductions in future hospitalization rates or requirement for surgery. Furthermore, cross-sectional abnormalities may exist even in the presence of normal endoscopic examination of the terminal ileum, and even in the absence of histological findings of active inflammation. In these circumstances, patients with normal endoscopy and histology but with persistent cross-sectional imaging alterations face a worse prognosis in terms of relapse, surgery requirements and hospitalizations. Therefore, cross-sectional imaging should be integrated in the definition of complete remission in association with endoscopy and histology.
In a different setting, CT and MRE has demonstrated a high diagnostic accuracy to detect strictures and penetrating complications such as fistulas and abscesses and have a high impact on patient management. Beyond the standard definition of stricture by CTE or MRE, another relevant aspect is the identification and quantification of fibrosis by imaging biomarkers. The proportion of patients developing intestinal strictures increases over the years after a diagnosis of CD and represents the main cause of damage progression and surgery in that group of patients. Different strategies based on MRE have been studied with the aim to detect and quantify the degree of fibrosis deposition, including diffusion-weighted imaging (DWI), magnetization transfer and delayed enhancement. However, recent data from a multicentric study suggests that only DWI shows a good correlation with the fibrosis in the bowel but also with inflammation. Thus, the contribution of additional imaging biomarkers such as the amount of creeping fat or modern stiffness quantification by MR elastography deserves further attention.

Rapidity of ozanimod-induced symptomatic response and remission in patients with moderately to severely active Ulcerative Colitis: Results from the induction period of True NorthECCO'22 Virtual
Year: 2022
Authors: Britta Siegmund
Background

Ozanimod, a sphingosine 1-phosphate (S1P) receptor modulator selectively targeting S1P1 and S1P5, is approved in the US for the treatment of moderately to severely active ulcerative colitis (UC). In the pivotal phase 3 True North randomised controlled trial in moderate-to-severe UC, significantly more patients (pts) achieved clinical response and remission with ozanimod vs placebo (PBO) at week (wk) 10 of the induction period. Here, we report the rapidity of ozanimod-induced symptomatic response and remission in pts from True North (NCT02435992).

Methods

In True North, pts were randomised to once-daily ozanimod 0.92 mg (equivalent to ozanimod HCl 1 mg) or PBO (Cohort 1) or received open-label ozanimod (Cohort 2) during induction. This analysis evaluated symptomatic response (defined as ≥1 point and ≥30% decrease from baseline in adapted partial Mayo score and ≥1 point decrease from baseline in rectal bleeding score [RBS] or absolute RBS ≤1) and symptomatic remission (defined as RBS of 0 and stool frequency score [SFS] ≤1 point and ≥1 point decrease from baseline at each study visit from wk 2 through 10.

Results

During induction, 645 pts were randomised to ozanimod (n=429) or PBO (n=216) in Cohort 1, and 367 pts received open-label ozanimod in Cohort 2. Baseline demographics and clinical characteristics were well balanced across groups. Differences in symptomatic response were observed between ozanimod and PBO recipients in Cohort 1 as early as 2 wk after ozanimod initiation (1 wk post-titration) for the overall population (36.1% vs 26.4%; difference: 9.6% [95% CI, 2.1–17.0]; Figure 1) and tumour necrosis factor inhibitor (TNFi)-naïve pts (38.5%, n=301 vs 29.1%, n=151; difference: 9.4% [95% CI, 0.2–18.5]), and as early as 4 wk for TNFi-exposed pts (42.2%, n=128 vs 27.7%, n=65; difference: 15.8% [95% CI, 1.8–29.8]). Differences in symptomatic remission were observed between ozanimod and PBO recipients in Cohort 1 as early as 5 wk after ozanimod initiation (4 wk post-titration) for the overall population (26.3% vs 16.7%; difference: 8.6% [95% CI, 1.8–15.4] Figure 2), as early as 4 wk for TNFi-naïve pts (27.2% vs 17.9%; difference: 9.4% [95% CI, 1.5–17.4]), and as early as 8 wk for TNFi-exposed pts (22.7% vs 12.3%; difference: 11.7% [95% CI, 1.3–22.1]). Rates of symptomatic response and remission in pts receiving open-label ozanimod (Cohort 2) were similar to those in pts receiving randomised ozanimod (Cohort 1).

Conclusion

In the overall population, ozanimod was associated with higher rates of symptomatic response and remission vs PBO as early as 2 and 5 wk, respectively, after treatment initiation. Both clinical endpoints were more rapidly achieved in TNFi-naïve vs TNFi-exposed pts.

Real World Effectiveness, Safety and Pharmacokinetics of Switching Intravenous Vedolizumab Maintenance treatment to Subcutaneous Vedolizumab Therapy for Inflammatory Bowel DiseaseECCO'22 Virtual
Year: 2022
Authors: Adriaan Volkers
Background

Subcutaneous (SC) formulation of vedolizumab (VDZ) is available for Crohn’s disease (CD) and ulcerative colitis (UC). We assessed the efficacy, safety, and pharmacokinetic (PK) profiles of patients with inflammatory bowel diseases (IBD) who switched from intravenous (IV) to SC VDZ treatment in two prospective, real world cohorts.

Methods

The primary cohort is an ongoing open-label, real life, prospective single centre cohort study. As a validation cohort, we used the Initiative on Crohn and Colitis (ICC) registry, a prospective, observational, nationwide registry including patients switching from IV to SC VDZ. In both cohorts, patients receiving IV VDZ maintenance for >4 months were offered to switch treatment to SC VDZ, 108 mg every 2 weeks. In the primary cohort, assessment of clinical, biochemical and PK parameters took place at baseline, at approximately 10 weeks following the switch and at the physician’s discretion thereafter. In the ICC cohort, follow up visits were at week 12 and 24. The primary endpoint was the proportion of patients discontinuing SC VDZ at week 24.

Results

In total, 78 (50 CD (64%) and 28 UC (36%)) and 54 patients (29 CD (54%) and 25 UC (46%)) were included in the primary and ICC cohort respectively (table 1). During follow up, 8 (10.3%) of the primary cohort and 6 (11.1%) patients of the ICC cohort stopped VDZ SC during follow-up time till week 24, after a median treatment duration of 18 (IQR=5-19) and 10 (IQR=7-15) weeks, respectively.  Treatment withdrawal was most often caused by adverse events (AE), in total for 8 out of 132 patients (6%) (table 2). Four patients had loss of response to SC VDZ. Three of these patients had biochemical disease activity at initiation of SC therapy. Reported AEs included headache and injection related reactions. The median VDZ concentration increased from 11 ug/mL (IQR=9.4-20) to 28 ug/mL (IQR=24.3-31.2, p<0.0001) and from 20 ug/mL (14.3-26.3) to 34.6 ug/mL (26.8-42.9) (p<0.01), between baseline and visit 1 in the primary and validation cohort, respectively (figure 1).




Conclusion

The present abstract reports real world experience of switching IV to SC VDZ maintenance treatment in IBD patients in two observational Dutch cohorts. VDZ concentrations were significantly higher after the switch to SC VDZ. A switch from IV to SC VDZ appears to be effective and safe. However, a proportion of patients switched back to IV VDZ due to injection related AEs.

Real-world multicenter comparison of effectiveness between tofacitinib and vedolizumab in patients with Ulcerative Colitis after failure to at least one anti-TNF agentECCO'22 Virtual
Year: 2022
Authors: Anthony Buisson
Background

Several therapeutic options are now available in ulcerative colitis after anti-TNF failure, but no data compared hitherto tofacitinib and vedolizumab.

We compared the effectiveness of tofacitinib and vedolizumab in UC patients with prior exposure ≥ 1 anti-TNF.

Methods

In this multicentre retrospective study, we consecutively included all adult UC patients with partial Mayo score > 2, with ≥ 1 prior anti-TNF agent and started either tofacitinib (10mg b.i.d ± decreased to 5 mg b.i.d from week 8 (W8)) or vedolizumab (300 mg IV at W0-W2-W6 -W14 [± additional W10]) between January 2019 and June 2021.

The primary endpoint was corticosteroid-free clinical remission or CFREM (partial Mayo score ≤ 2) at W16. Secondary endpoints were endoscopic improvement (CFREM + endoscopic Mayo score ≤ 1) and mucosal healing (CFREM + endoscopic and histological remission defined as Nancy index ≤ 1).

All the comparisons were performed using propensity score analyses (inverse probability of treatment weighting) adjusted on gender, smoking, UC duration and extent, number of prior biologics or prior primary failure to biologics, concomitant 5-ASA, steroids or immunosuppressive agents, and disease severity.

Results

Overall, 400 patients will be included. Among the 200 first patients, 87 and 112 received tofacitinib and vedolizumab, respectively (one missing patient). Except for more pancolitis (54.0% vs 38.4%, p=0.028), less immunosuppressive therapies (4.6% vs 27.7%, p < 0.001), and higher rate of prior exposure ≥ 2 biologics (87.4% vs 37.5%, p < 0.001) in tofacitinib arm, baseline characteristics were similar across the two groups including concomitant 5-ASA (10.3% vs 18.8%) and steroids (23.0% vs 31.2%). Vedolizumab infusion at W10 was performed in 34.3% while 42.5% received tofacitinib 10 mg b.i.d until W16.

CFREM was achieved in 54.2% and 42.5% in tofacitinib and vedolizumab, respectively p=0.089). The rate of CFREM at W16 was 57.4% vs 51.1% (p=0.77) after one biologic, 55.4% vs 41.8% (p=0.61) after 2 biologics, 56.9% vs 6.3% (p=0.007) after at least 3 biologics, and 59.0% vs 33.3% (p=0.17) in the subgroup with partial Mayo score ≥ 6, in tofacitinib and vedolizumab groups, respectively.

Tofacitinib was more effective than vedolizumab to achieve CFREM at W16 in patients with primary failure to at least biologic (71.6% vs 30.8%, p=0.049).

Among 177 patients, endoscopic improvement was higher in patients treated with tofacitinib (33.6 % vs 7.1%, p=0.048). Mucosal healing was observed in 6.4% vs 3.8% in tofacitinib and vedolizumab arms, respectively (p=0.27).

Conclusion

Tofacitinib and vedolizumab are effective after failure to anti-TNF agents. Tofacitinib seems to be more effective in case of primary failure to biologics and multiple therapeutic failure.

Relationship, sexuality and family planning16th N-ECCO Network Meeting
Year: 2022
Authors: Simona Fourie
Summary content

1. To understand why relationships, intimacy and sexuality are important to those living with IBD
2. To discuss the sexual well-being concept
3. To review the current evidence on sexual well-being concerns from patient perspective
4. To review the current evidence of meeting sexual well-being and family planning care needs
5. To have an overview of optimal strategies to provide holistic care incorporating aspects of sexual well-being

Remission: How deep?8th ClinCom Workshop
Year: 2022
Authors: Shaji Sebastian
Summary content

 
 1.  To introduce changing targets for remission 

  2. To discuss  impact of `deep` remission in UC and CD

  3.  Describe challenges to meeting new targets 

Remote monitoring of biomarkers8th ClinCom Workshop
Year: 2022
Authors: Patrick Van Rheenen
Summary content

In asymptomatic patients with inflammatory bowel disease, monitoring involves repeated testing aimed at early recognition of a disease flare. The ultimate goal is to restore disease remission as early as possible and to prevent disease progression. Commonly used biomarkers to assess IBD activity include C-reactive protein (CRP) and fecal calprotectin (FC).

Classically, these diagnostic tests are performed in hospital laboratories where quality-control procedures apply. Recently, FC home testing has become available, allowing patients to measure IBD activity themselves. To establish a remote monitoring service that provides reliable results for correct clinical decision-making, a number of essential quality criteria must be met. In this presentation I outline the principles to good remote monitoring and illustrate those principles with an example from practice.

 

Educational objectives: 

1. To discuss 10 things to know before starting a remote monitoring service
2. To understand that setting up a remote FC monitoring service requires cooperation between health professionals, laboratory and medical IT specialists.
3. To emphasise that measuring biomarkers without accepting the consequences of the result is a waste of money.

Remote monitoring of IBD patients - challenges and future perspectives (Tandem talk)8th ClinCom Workshop
Year: 2022
Authors: Herbert Tilg; Nelly Teix
Summary content

Educational Objectives:


1. Definition of remote monitoring

2. Patient´s view: what would I expect

3. Early relevant telemedicine IBD papers

4. Role of calprotectin (point of care testing, POCT)

5. Does POCT affect medical therapy?

6. Lipocalin 2: a new fecal stool marker in IBD?

7. Patient´s view: where do I see the future?

8. Remaining challenges

Research Application preparation in practice7th N-ECCO Research Forum
Year: 2022
Authors: Wladyslawa Czuber-Dochan; Susanne Jäghult
Summary content

Educational objectives:
1. To understand the process of research application preparation
2. To have an overview of good research application for funding
3. To have an overview of the research funder's requirements 

4. To continue the networking in the Senior group of nurses in research
5. To find different kind of collaborations in the group

Research Award Outcomes 20207th N-ECCO Research Forum
Year: 2022
Authors: Katarina Pihl Lesnovska
Summary content

Educational objectives: 

1. To develop a Patient-reported outcome measures (PROM) to assess disease activity in microscopic colitis (MC) fulfilling the requirements of the Food and Drug Administration (FDA).

The European Microscopic Colitis Activity Index (E-MCAI) was developed in four steps: 1) A list of symptoms associated with active MC was created by a group of experts in the field. 2) Content validity of the symptoms was performed by experts (n=14) and patients (n=79) using the Content Validity Index. 3) Questions and response alternatives were created for each symptom, and validity of the E-MCAI was evaluated with cognitive interviews with patients (n=7) and by the experts. 4) A pilot postal survey was performed to ensure usability.

Seven of the symptoms related to active MC fulfilled the criteria for content validity and were included in the E-MCAI: stool consistency, stool frequency, stools at night, feel a need to pass more stools shortly after a bowel movement, urgent need to empty the bowel, leakage of stool, and abdominal pain. The development and validation process resulted in the current version of the E-MCAI consisting of six questions related to MC.

The E-MCAI was developed using the methods advocated by the FDA. The evaluation indicates good content validity. Further evaluation will be performed to accomplish construct validity, reliability, and responsiveness in future cross-sectional and longitudinal studies.

Research Award Outcomes 20207th N-ECCO Research Forum
Year: 2022
Authors: Simona Fourie
Summary content

Educational objectives: 

1. To develop a Patient-reported outcome measures (PROM) to assess disease activity in microscopic colitis (MC) fulfilling the requirements of the Food and Drug Administration (FDA).

The European Microscopic Colitis Activity Index (E-MCAI) was developed in four steps: 1) A list of symptoms associated with active MC was created by a group of experts in the field. 2) Content validity of the symptoms was performed by experts (n=14) and patients (n=79) using the Content Validity Index. 3) Questions and response alternatives were created for each symptom, and validity of the E-MCAI was evaluated with cognitive interviews with patients (n=7) and by the experts. 4) A pilot postal survey was performed to ensure usability.

Seven of the symptoms related to active MC fulfilled the criteria for content validity and were included in the E-MCAI: stool consistency, stool frequency, stools at night, feel a need to pass more stools shortly after a bowel movement, urgent need to empty the bowel, leakage of stool, and abdominal pain. The development and validation process resulted in the current version of the E-MCAI consisting of six questions related to MC.

The E-MCAI was developed using the methods advocated by the FDA. The evaluation indicates good content validity. Further evaluation will be performed to accomplish construct validity, reliability, and responsiveness in future cross-sectional and longitudinal studies.

Research Award Presenter 20227th N-ECCO Research Forum
Year: 2022
Authors: Rosanna Irene Comoretto
Summary content

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.

Research Award Presenters 20217th N-ECCO Research Forum
Year: 2022
Authors: Martha van Gaalen; Merel Van Pieterson
Summary content

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.

Risankizumab maintenance therapy results in sustained improvements in endoscopic outcomes in patients with moderate to severe Crohn’s Disease: Post-hoc analysis from the phase 3 study FORTIFYECCO'22 Virtual
Year: 2022
Authors: Peter Miles Irving
Background

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

Methods

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.

Results

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



Conclusion

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  

Role of adherent and invasive E. coli in Crohn’s Disease: Lessons from the postoperative recurrence modelECCO'22 Virtual
Year: 2022
Authors: Anthony Buisson
Background

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.

Methods

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).

Results

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.

Conclusion

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

Safety after all6th Basic ECCO: EduCational COurse for Industry
Year: 2022
Authors: Laurent Beaugerie
Summary content

The educational objectives of the presentation are:
1. To understand that the choice of long-term treatment of IBD must take into account the benefit-risk balance of old and new IBD drugs
2. To review the most important aspects of IBD drug-induced cancers and serious infections
3. To understand that in most cases benefits outweigh risks, and that patients should not be undertreated
4. To understand, based on the example of tofacitinib, that it is important keep prudent with recently approved IBD drugs until powered data is available

After introducing the concept of benefit-risk balance, the presentation will review the three major aspects of IBD drug potential complications: drug-class specific complications, malignancies, and serious infections, including opportunistic infections.  A special focus will be made on thiopurine-induced lymphomas, thiopurine and anti-TNF-induced serious bacterial and viral infections, and how to manage these risks. We will then discuss the difficult choice of immunosuppressants in frail and older patients, based on drug-class specific safety data. Finally, using the example of tofacitinib, we will illustrate the importance of prescribing with caution recently approved drugs, until we have extensive safety data.

Scoring activity and response in CD and UC9th ECCO Ultrasound Workshop - Advanced in collaboration with ESGAR
Year: 2022
Authors: Rune Levring Wilkens
Summary content

Educational objectives:
1. To understand the ultrasound features that represent disease activity in CD and UC
2. To get an overview of existing activity scores in CD and UC
3. To get an overview of transmural healing
4. To know the advantages and challenges by applying activity scores.

Second clinical case11th S-ECCO IBD Masterclass
Year: 2022
Authors: Carolynne Vaizey
Segmental vs Total Colectomy for Crohn’s Disease of the colon in the biologic era. Results from the SCOTCH international, multicentric studyECCO'22 Virtual
Year: 2022
Authors: Gianluca Pellino
Background

Previous studies suggested a role for segmental colectomy (SC) and total colectomy (TC) for colonic Crohn’s disease (cCD). TC might reduce recurrence rates, at the cost of impaired quality of life and higher stoma rates. We compared the long-term outcomes of SC and TC.

Methods

This is an international, multicentric study on data from the prospective databases of six centres. All consecutive patients operated on between 2000 and 2019 for cCD with SC or TC were included. Exclusion criteria were colorectal cancer, previous bowel resections, and lack of follow-up data. Disease extension was based on involvement of 1 to 5 colonic segments. Resection of 1-3 segments was classified as SC, resection of 4-5 segments as TC. Primary aim was surgical recurrence after SC vs TC. Secondary aims were perioperative complications, stoma formation rate, and predictors of recurrence.

Results

Data of 687 (56.2% women) patients were analysed. Mean age at diagnosis and at surgery were 30±15.8 and 40.4±15.4 years. Disease duration was 10.4 ± 8.6 years. 16.6% of patients were A1, whereas most (62.2%) were diagnosed between 17 and 40 years. Isolated cCD (L2) was present in 61.1%, ileocolic CD (L3) in 38.9%, and concomitant jejuno-ileal CD (L4) in 3.2%. Most had stricturing (B2) cCD (41.9%). Active perianal disease was found in 28.9% patients. SC was performed in 285 patients, TC in 402. The latter more frequently had isolated cCD, inflammatory (B1) disease, current (37.8 vs 16.5%, p<0.001) or previous (56 vs 32.6%, p<0.001) perianal CD, and longer disease duration (11.3 ± 8.9 vs 9.2 ± 7.9, p<0.001). Postoperative complications and mortality were similar, but TC patients more frequently required 90-day readmission (6% vs 2.1%, p=0.02). Temporary (31.6 vs 21.4%, p<0.001) and definitive (39.3vs8%, p<0.001) stomas were more likely after TC. The 15-year cumulative surgical recurrence was 36%, more likely in the TC group (44 vs 27%, Log-Rank p=0.006), and it was not affected by the number of colonic segments involved (23 vs 28%, 1-3 vs 4-5 segments p=0.2) (Fig 1). In patients with 1-3 segments involved, postoperative treatment with biologics, compared to any other regimen, reduced the risk of recurrence (25 vs 51%, p<0.001), while early age at diagnosis (p=0.02) and perianal CD (p=0.01) increased the risk. Omission of biological therapy (HR 5.4, 95%CI 5.1-5.8 p<0.001), and paediatric diagnosis (HR 2.1, 95%CI 2.3-3.1 p<0.001) were the strongest predictors of recurrence in this subgroup.


Conclusion

In this study, SC was safe, required less frequently stoma and repeated surgery, compared with TC. These findings question previous data on the topic and might be supported by the efficacy of postoperative biologic therapy on cCD.