bluuebunny/crossref_metadata_2025 huggingface dataset:
P090 Risk of Rectal Cancer after Colectomy in Patients with Inflammatory Bowel Disease – A Nationwide Population-based Danish Cohort Study 1978–2018
Authors: Akimenko E , Bjerrum J T , Allin K H , Iversen A T , Jess T
Published: May 2021

Background

The risk of surgery remains high both among patients with ulcerative colitis (UC) and patients with Crohn’s disease (CD) with a cumulative risk of subtotal colectomy with ileostomy and diverted rectum of 7.5% after 5 years in UC and a similar risk in CD.

Ileostomy with diverted rectum after colectomy may be permanent, or the patient can undergo restorative surgery with ileo-rectal anastomosis (IRA) or ileal pouch-anal anastomosis (IPAA).

Risk of rectal cancer in this patient population remains uncertain.

We performed a nationwide population-based Danish study of rectal cancer (RC) risk after subtotal colectomy.

Methods

Through the Danish Civil Registration System, a source population of all individuals 15 years or older living in Denmark between 1978 and 2018 was retrieved. By use of the unique personal identification number given to all citizens at birth, this source population was linked to the Danish National Patient Registry (NPR) in order to identify all patients with inflammatory bowel disease (IBD). Patients with a diverted rectum, IRA or IPPA after colectomy were also identified with NPR. Cases of RC were identified in the Danish Cancer Registry. Patients with IBD were followed from the date of surgery until cancer, emigration, death or end of the study.

The risk of RC in patients with diverted rectum was assessed using Cox regression analyses, as compared to the background population as well as to subjects with IBD without subtotal colectomy.

Results

RC occurred in 42 (0.9%) of 4931 patients after subtotal colectomy with diverted rectum, compared to 209 (0.4%) of 49,251 in the matched IBD cohort with no colectomy and 941 (0.4%) of 246,550 in the matched background population.

In the IBD and subtotal colectomy population 11 (26%) of the 42 cases were in patients diagnosed with CD and 31 (74%) were in patients with UC.

The hazard ratio (HR) for RC in IBD patients with diverted rectum vs. matched IBD patients without colectomy (adjusted for IBD type and sex) was 0.80 (95% CI 0.29, 2.17) during the first 10 years of follow-up and 7.93 (95% CI 5.48, 11.48) 10 years or more after colectomy. Likewise, the HR for RC in IBD patients with diverted rectum compared to the matched background population was 0.85 (95% CI 0.32, 2.28) during the first 10 years of follow-up and 10.25 (95% CI 7.36, 14.28) 10 years or more after colectomy.

Conclusion

In our nationwide population-based cohort study covering years 1978–2018 we observed an 8 to 10-fold increased risk of RC of the diverted rectum 10 years after colectomy.These data suggest a need for developing a specific surveillance strategy for this group of IBD patients.
P113 Automatic detection of colonic ulcers and erosions in colon capsule endoscopy images using a convolutional neural network
Authors: Ribeiro T , Mascarenhas Saraiva M , Afonso J , Cardoso H , Ferreira J , Andrade P , Jorge R , Lopes S , Macedo G
Published: May 2021

Background

Conventional colonoscopy is gold standard for the diagnosis and monitoring of patients with suspected or known inflammatory bowel disease (IBD). Nevertheless, it is a potentially painful procedure with risk of complications, including bleeding and perforation. Colon capsule endoscopy (CCE) is a minimally invasive alternative for patients unwilling to undergo colonoscopy or when it is contraindicated or unfeasible. However, CCE produces thousands of frames and their revision is a time-consuming and monotonous task.

The detection of ulcers and erosions is paramount for the diagnosis and assessment of the activity of IBD. However, these lesions may appear in a very small number of frames, thus increasing the risk of overlooking significant lesions.

Our aim was to develop an Artificial Intelligence (AI) algorithm, based on a multilayer Convolutional Neural Network (CNN) for automatic detection of ulcers and erosions in CCE exams.

Methods

A total of 24 CCE exams (PillCam COLON 2®) performed at a single centre between 2010–2020 were analysed. From these exams, 3 635 frames of the colonic mucosa were extracted, 770 containing colonic ulcers or erosions and 2 865 showing normal colonic mucosa. These images were used for construction of training (80% of the frames) and validation (20% of the frames) datasets. For automatic identification of these lesions, these images were inputted in a CNN model with transfer learning. The output provided by the CNN (Figure 1) was compared to the classification provided by a consensus of specialists. Performance marks included sensitivity, specificity, positive and negative predictive values, accuracy and area under the receiving operator characteristics curve (AUROC).

Results

After the optimization of the neural architecture of the CNN, our model automatically detected colonic ulcers and erosions with a sensitivity of 90.3%, specificity of 98.8% and an accuracy of 97.0% (Figure 2). The AUROC was 0.99 (Figure 3). The mean processing time for the validation dataset was 11s (approximately 66 frames/s).

Conclusion

We developed a CNN model which demonstrated high levels of efficiency for the automatic detection of ulcers and erosions in CCE images. Our study lays the foundations for the development of effective AI tools for application to CCE exams. These systems may enhance the diagnostic accuracy and reading efficiency of CCE, thus expanding the role of minimally-invasive colonic exploration in the management of IBD patients.
P116 Development of a new patient-reported outcome measure for patients with complex cryptoglandular fistulas
Authors: McCurdy J , Crooks P , Gwaltney C , Krupnick R , Cadogan K A , Gonzalez S , Karki C
Published: May 2021

Background

Complex cryptoglandular fistulas (CCF) arise from infected anal glands and are often associated with substantial morbidity and healthcare utilization. Standarized patient-reported outcome measures (PROMs) for CCF are lacking. Thus, we aimed to develop a disease-specific PROM to assess the burden of symptoms and their impact on daily life in patients with CCF.

Methods

To develop a conceptual model, a targeted literature review was conducted to identify symptoms and impacts on daily life associated with CCF. Existing PROMs relating to anal fistulas were also sought. Semi-structured interviews with colorectal surgeons (n=5) assessed clinical perspectives on patient experience of CCF. A draft item pool was developed based on the refined conceptual model and using the Quality of Life in Patients with Anal Fistula Questionnaire as a reference. The tool was refined through concept elicitation interviews on the symptoms and impacts of CCF, and cognitive debriefing on the interpretation, understanding and response to each item. Interviews were conducted until concept saturation was achieved and patient feedback suggested no further refinements were required.

Results

The literature review identified discharge, pain, faecal incontinence and bleeding as the most prevalent symptoms, and embarrassment as the most prevalent impact on daily life. Results from surgeon interviews were then used to revise the initial conceptual model. Twenty US adults (60% female; mean age, 49 years) with clinically confirmed CCF participated in interviews (four waves of n=5). Patients identified 10 salient symptoms and 11 salient impacts on daily life (salient defined as mention by ≥50% of patients and mean disturbance rating ≥5 on a 10-point scale). The final conceptual model included the main symptoms and treatment-related effects, and impacts on daily life. The draft item pool was refined, resulting in a final PROM consisting of 14 items (covering frequency and severity) relating to symptom domains – discharge, incontinence, pain, irritation, odour, abscess – and 6 items relating to health-related quality of life domains – functional, physical, psychological, social health. The PROM features a 7-day recall period, with responses mostly given on a 5-point verbal rating scale. Cognitive debriefing confirmed that the PROM was clear, easy to understand and relevant to patients’ experiences.

Conclusion

The 20-item CCF questionnaire (CCFQ-20) is a new PROM that has been developed and tested for content validity, following expert guidance and regulatory best practices. It addresses a comprehensive set of salient symptoms and impacts experienced by patients with CCF. Psychometric testing is required to fully evaluate this PROM.

Sponsor: Takeda Pharmaceuticals USA, Inc.
P130 Adhesions are not always the enemy: pouch volvulus
Authors: Dionigi B , Lavaryk O , Lightner A , Holubar S , Hull T
Published: May 2021

Background

Proctocolectomy with ileal pouch anal anastomosis (IPAA) was introduced over 40 years ago, prior to the era of laparoscopy. Minimally invasive surgery (MIS) techniques have been applied to pelvic pouch surgery. One advantage of MIS is the reduction in adhesion-related complications. The lack of adhesions may result in different complications. When the pouch is not adherent in the pelvis, pouch volvulus can occur around the mesenteric axis. The aim of this study was to describe our experience with pelvic pouch volvulus.

Methods

Our prospectively maintained pelvic pouch registry and our enterprise wide electronic medical record were queried for keyword combinations of “pouch volvulus” between 1994 and 2020. Pouch volvulus was defined as torsion of the ileal pouch on its mesenteric axis or around small bowel maintaining the proper orientation of the ileo-anal anastomosis. Patients with pouches constructed with twisted mesenteric axis from ill-aligned anastomoses were excluded. Data for these patients was collected from the pouch registry and additional chart review.

Results

We identified 17 patients with pouch volvulus; of these, 11 patients did not meet our selection criteria and were excluded. Of the 6 patients (5 female; median age 25) with true volvulus, the diagnosis at IPAA was ulcerative colitis (n=5) and Lynch syndrome with a rectal cancer. All pelvic pouches were constructed with MIS techniques, including standard laparoscopy (n=4) and single incision laparoscopic technique (n=2). All 6 patients presented with diffuse abdominal pain and abdominal distention. The average time from pouch construction to pouch volvulus was 2.5 years (range: 5.2 – 97.5 months). Computed tomography with or without rectal contrast was the initial diagnostic test in 4/6 with findings highly suspicious for pouch volvulus. Surgery was performed urgently in 5/6 of patients; all 6 had open surgery. At reoperation, all had minimal adhesions and a gap between the pouch mesentery and the retroperitoneum. Interventions included pouch-pexy (n=3), closure of gap between pouch and sacrum (n=2), and pouch excision and ileostomy (n=1). At a median of 9 months (IQR: 4–97) of follow up, pouch survival was 83%; functional outcomes included mild fecal incontinence (n=1) and paradox requiring intermittent pouch intubation for stool evacuation (n=1).

Conclusion

Pelvic pouches constructed by minimally invasive techniques may be at risk for pouch volvulus due to minimal adhesions. Surgeons should have a high index of suspicion for patients with unexplained abdominal pain, distension, and other obstructive symptoms. Cross-sectional imaging with rectal contrast, may help clarify the diagnosis. Immediate surgical care can allow for pouch salvage.
P156 Translation into Spanish, adaptation and validation of the “IBD- control”, a short validated English PRO (patients reported outcomes) questionnaire: the EII-Control
Authors: Vicente Lidon R , García S , Corsino P , Boudet J M , Sierra E M , García P , Sanz P , Gomollón F
Published: May 2021

Background

The measure of patient reported outcomes (PROM) in inflammatory bowel disease (IBD) clinical practice, is hardly to use as it lacks a simple and valid tool. There is a short, generic and validated English questionnaire for this purpose: the IBD Control. Its validation and application in other IBD populations is necessary and would support its practical use. Our purpose is to translate into Spanish, adapt and validate the “IBD- control” in our ambit and culture, in order to have a useful measure for clinical practice.

Methods

The IBD-control was translated into Spanish, demonstrating its understandability, content, validity and acceptability for patients, generating the EII-Control instrument. Subsequently, the EII-Control was prospectively validated, using current psychometric standards. At the baseline visit, consecutive patients completed the EII-Control, the short form of IBD quality of life (QOL) questionnaire (CVEII-9), the generic QOL instrument (EQ-5D), the hospital anxiety and depression scale (HDA and HDS), the fatigue questionnaire (FSS), as well as a clinical assessment, blind to the questionnaires (global clinical rating, Harvey-Bradshaw indice or simple index of clinical activity of colitis (SSCAI) and treatment outcome). A subgroup of patients repeated the assessment on a second visit within the study period. The usefulness of summary scales of the IBD-Control, was also analyzed (EII-Control-8 and EII-control-VAS).

Results

249 patients completed the baseline surveys (Crohn’s disease, n = 177; ulcerative colitis, n = 71 and indeterminate colitis, n = 1) and 101 repeated the same assessment on a second routine visit. Internal consistency: Cronbach’s for EII-control 0.83 with strong correlation between EII-Control-8 and EII-Control-VAS subscales (r = 0.5). Reproducibility: intraclass correlation = 0.70 for EII-Control and 0.61 for EII-Control-VAS. Construct validity: moderate to strong correlations between EII-Control versus activity, anxiety, depression, fatigue or quality of life indices Discriminant validity: (mean scores of the instruments for remission, mild, moderate or severe): p <0.001. Sensitivity to change: same response in effect size and mean differences as CCVEII-9. Sensitivity and specificity at cut-off 14 of 0.696 and 0.903 respectively to determine the quiescent state.

Conclusion

The EII-Control is a rapid, reliable, valid and sensitive instrument to measure the overall control of the disease from the perspective of the patient in spanish culture. Its simplicity, ease of use, and generic applicability make it a candidate for supporting routine care, including telemedicine, and also to use in clinical research.
P200 Celiac disease (CD) and CHRONIC INFLAMMATORY BOWEL DISEASE (IBD) association
Authors: Hmimass S , Benelbarhdadi I , Lagdali N , Borahma M , Ajana F Z
Published: May 2021

Background

Association Celiac disease (CD) and CHRONIC INFLAMMATORY BOWEL DISEASE (IBD) is rare. the aim of the study is to determine the frequency as well as the anatomical and evolutionary characteristics of this association.

Methods

This is a retrospective descriptive and analytical study of 10 patients between 2005 and 2020. The diagnosis of CD was established after careful clinical examination and questioning, on the determination of specific auto antibodies against transglutaminase type Ig A and endomysium and on the histological study of duodenal biopsies showing a IEL> 30%. And that of IBD was based on a range of clinical, endoscopic, histological and radiological arguments

Results

10 cases of association CD and IBD were diagnosed in a cohort of 267 CD, 960 Crohn’s disease and 520 Haemorrhagic rectocolitis. The frequency of association was 3.7% in the cohort of CD, 0.9% In the Crohn’s disease cohort and 0.2% in the cohort of Haemorrhagic rectocolitis. Predominantly female, 80% female and 20% male. The diagnosis of CD preceded that of Crohn’s disease in 80% (n=8), with an average delay of 32 months (12–72 months). All patients were put on a gluten-free diet (GFD). Despite good therapeutic compliance for at least 18 months, the evolution was marked by the persistence of anaemic syndrome and dysenteric syndrome in six cases (60%), diarrhoea and colic-type abdominal pain in four cases (40%). And an occurrence of rectorragie, anaemic syndrome and dysenteric syndrome in two cases (20%). In front of the persistence of symptoms, we first eliminated a resistance to GFD. Then an upper and lower digestive, radiological and histological endoscopic assessment concluded that there was an isolated colonic crohn’s disease in five (50%) of the patients; gastric and colonic in three (30%). 60% (n=6) of the patients had luminal and stenotic involvement in two patients. The diagnosis of IBD preceded that of celiac disease in 20% (n=2), one patient had luminal colonic Crohn’s disease and one patient had left Haemorrhagic rectocolitis. The diagnosis of CD was clinically retained by the appearance of an associated anemic syndrome in one case with atypical abdominal pain, and with dysenteric syndrome in the other case. Serologically, one was positive for anti transglutaminase type Ig A and the other was seronegative. Histologically, both patients had a IEL >30% with subtotal atrophy. The evolution was favourable on the GFD, which was always followed up alongside the treatment of IBD, with good clinical and endoscopic improvement

Conclusion

The association between CD and IBD is possible, albeit rare. It is necessary to think about the search for it whenever there is a persistence or appearance of other evocative symptoms despite good therapeutic compliance.
P220 Patient-entered symptoms scores collected using a new IBD patient portal correlate closely with clinical assessment and can optimise delivery of IBD care
Authors: Carlson S , Harrow P , McCartney S
Published: May 2021

Background

Patient healthcare portals can empower IBD patients by allowing access to their electronic health record and provide opportunities for active participation in their care.

We built 3 patient-entered symptom questionnaires in EPIC MyChart using existing validated IBD symptom scores (HBI, SCCAI, IBD Control). Patients were invited to complete these prior to clinic using the MyChart patient portal. In this study we examine the feasibility and accuracy of patient entered scores compared to the physician’s impression of disease activity and the potential impact on healthcare delivery.

Methods

Between September 2020 and January 2021 consecutive patients were invited to complete 2 questionnaires reporting disease activity on the EPIC MyChart portal using the IBD Control (Bodger et al. 2014) and either HBI or SCCAI (for Crohn’s disease and UC respectively). Only patients who completed these scores were included in this study. A retrospective review of the notes was completed to determine the physician’s impression of disease activity and actions taken by the physician in the outpatient clinic.

Results

107 patients with Crohn’s and 80 with UC were included in the study. 60% of CD and 56% of UC patients were in remission by HBI (<5) or SCCAI (<3). Patient reported disease activity correlated well with clinical impression of disease activity. 88% of CD patients and 98% of UC patients in HBI or SCCAI remission were also deemed to be in remission on physician’s clinical impression (r= 0.54, p <0.001 and r= 0.74, p <0.001). Both CD and UC had lower rates of remission by IBD Control (49% and 53%). This score also captures fatigue and mood. Furthermore, the IBD Control identified a specific question to be addressed at the upcoming clinic visit for 76% of patients with CD and 64% with UC.

Importantly, 24% of all UC patients (n=19) in remission by SCCAI and IBD Control, had no questions they wanted addressed, and all of these patients had no further actions triggered by clinic attendance. Conversely in the 18% patients with moderate to severe disease by HBI or SCCAI, 50% required a blood test or calprotectin prior to further clinical decisions.

Conclusion

Patient-entered symptom scores correlate closely with physician’s impression of disease activity and patients are able to accurately record these using the EPIC MyChart portal. Importantly, it is possible to identify a cohort of patients who are well, where there are opportunities to optimise follow-up, and conversely a group of patients with active disease where key investigations can be arranged prior to clinical review to prevent delays in treatment. These patients can also be prioritised for face-to-face clinics, at a time when reducing social contacts is imperative.
P250 Does Ethnicity Influence Patient’s Preferences for Treatment Outcome? The Israeli Experience
Authors: Broide E , Richter V , Mari A , Khoury T , Shirin H , Naftali T
Published: May 2021

Background

IBD behaves differently among different ethnic groups. Patients perceptions and priorities for treatment outcome may well be influenced by their culture and beliefs. However, data on the impact of ethnicity on IBD patient’s attitude and expectation for treatment outcomes are still scares. We aimed to compare patient’s preferences and priorities for treatment outcomes among Jewish and Muslims IBD patients in Israel.

Methods

A prospective survey was conducted among Muslims IBD patients and compared to historical data set of Jewish IBD patients. Data included demographics and socioeconomics parameters as well as clinical data. Patients were asked to rank ten items regarding their preferences for treatment outcome, based on the ten IBD disk items. Cluster analysis was used to classify both patient’s groups into homogeneous subgroups according to their preferred IBD items.

Results

391 patients were included in our analysis; 121 Muslims patients were compared to historical data base of 240 Jewish patients, 67.9% CD patients and 33.5% UC patients. Both groups were similar regarding age, disease activity and treatment, but the duration of disease was longer in the Jewish population (a median of 9 vs 6 years, p=0.01). As a group, Muslim patients ranked the priorities for treatment outcome lower compared to the Jewish population. The items with the highest priority were the same in both groups with abdominal pain, energy, and regular defecation ranking highest. There were no differences between Muslims men and women, but the Jewish women attached higher priority to abdominal pain, energy, sleep, joint pain, education and work. The cluster with the higher scores was characterized by more females (p<0.001), Jews (p<0.001), urban residency (p<0.001), working hours per week (p=0.003), lower income (p= 0.011) CD patients (p=0.011), active disease (p<0.001), and lower response to treatment (p=0.002). Multivariable regression analysis revealed an association between higher patient’s ranking and Jewish religion (OR 4.77) male gender (OR 0.5), income level (OR 0.2), active disease (OR 5.29) and CD (OR 0.4).

Conclusion

The ethnic difference has a high impact on patient’s ranking of priorities for treatment outcome. These differences can be explained by socioeconomic factors. Despite the ethnic and cultural differences, symptoms relief is in the highest priority in both patient groups.
P284 Drug survival and remission rates in ustekinumab treated ulcerative colitis: Results from the Swedish Inflammatory Bowel Disease register (SWIBREG)
Authors: Thunberg J , Björkqvist O , Olén O , Ludvigsson J F , Eriksson C , Halfvarson J
Published: May 2021

Background

Randomised controlled trials may not correctly reflect clinical practice. We aimed to assess the clinical effectiveness of ustekinumab in a real-world cohort of patients with ulcerative colitis (UC).

Methods

This observational, multi-centre cohort study explored ustekinumab treated patients with UC from the Swedish inflammatory bowel disease register (SWIBREG), a nationwide quality register. Prospectively collected clinical data were extracted December 2020. The primary outcome was the 16-week ustekinumab continuation rate. Secondary outcomes included A) drug continuation rate at the end of follow-up, B) corticosteroid-free biochemical remission, defined as f-Calprotectin<250µg/g, and C) corticosteroid-free clinical remission per patient-reported Mayo score, i.e. a rectal bleeding subscore <1 and a stool frequency subscore ≤1 and not greater than baseline. Continuous data are presented as median and (interquartile range). Differences between baseline and follow-up visits were assessed by the Wilcoxon signed-rank test.

Results

In total, 145 patients were included and followed for a median period of 32 (19-56) weeks. Baseline characteristics are presented in Table 1. The drug continuation rate was 87% (126/145) at 16 weeks and 69% (100/145) at end of follow-up (Figure 1-2). Corticosteroid-free clinical and biochemical remission rates at follow-up visits are shown in Figure 3. The 6-point Mayo score decreased from 5 (3-6) at baseline to 2 (2-4) at 16 weeks (p<0.01) and to 3 (2-4) at last follow-up (p<0.01). F-calprotectin levels decreased from 779 (252-1530) µg/g to 246 (56-844) µg/g at week 16 (p=0.02) and to 142 (36-935) µg/g at last follow-up (p<0.01).

Conclusion

Ustekinumab was associated with clinical effectiveness in this nationwide real-world treatment refractory cohort.
P286 Ustekinumab for Crohn’s Disease: Two-Year Results of the Initiative on Crohn and Colitis (ICC) Registry, a Nationwide Prospective Observational Cohort Study
Authors: Straatmijer T , Biemans V B C , Hoentjen F , de Boer N K H , Bodelier A G , Dijkstra G , van Dop W , Haans J J L , Jansen J M , Maljaars P W J , van der Marel S , Oldenburg B , Ponsioen C Y , Visschedijk M C , de Vries A C , West R , van der Woude C J , Pierik M , Duijvestein M , van der Meulen- de Jong A E
Published: May 2021

Background

Ustekinumab is a monoclonal antibody that selectively targets p40, a shared subunit of the cytokines interleukin (IL)-12 and IL-23. It is registered for the treatment of Crohn’s disease (CD) and ulcerative colitis. We assessed the two-year efficacy and safety of ustekinumab in a real world, prospective cohort of CD patients.

Methods

CD patients who started ustekinumab in regular care were prospectively enrolled in the nationwide Initiative on Crohn and Colitis Registry. At week 0, 12, 24, 52 and 104, clinical remission (HBI ≤ 4 points), biochemical remission (fecal calprotectin (FC) ≤200 μg/g and/or CRP ≤5 mg/L), peri-anal fistula remission, extra-intestinal manifestations, ustekinumab dosage and safety outcomes were determined. Patients starting therapy less than two years ago were excluded for the current evaluation. The primary outcome was corticosteroid-free clinical remission at week 104.

Results

In total, 252 CD patient with at least two years of follow up were included. Of all included patients, the proportion of patients in corticosteroid-free clinical remission at week 12, 24, 52 and 104 was 32.3% (81/251), 41.4% (104/251), 39% (97/249) and 34.0% (84/247), respectively. Of the 97 patients in corticosteroid free clinical remission at week 52, 58 (59.8%) were still in corticosteroid-free clinical remission at week 104. In patients with combined clinical and biochemical disease activity at baseline (n=122), the corticosteroid-free clinical remission rates were 23.8% (29/122), 35.2% (43/122), 40.0% (48/120) and 32.8% (39/119) at week 12, 24, 52 and 104, respectively. The probability of remaining on ustekinumab treatment after 52 and 104 weeks was 64.3% and 54.8%, respectively. There were no predictive factors associated with corticosteroid-free clinical remission at week 104 on univariate and multivariate analysis. Most common adverse events were headache, skin reaction and musculoskeletal complaints. Two patients stopped ustekinumab due to an infection after 8 and 30 weeks of treatment (mild fever syndrome and moderate upper airway infection, respectively). The main reason for discontinuing treatment after 52 weeks was loss of response (66.7%).

Conclusion

Ustekinumab was effective and relatively safe in our real world, prospective cohort of CD patients. After 104 weeks of ustekinumab treatment, one third of patients were in corticosteroid-free clinical remission.
P293 Local Mesenchymal Stem Cells injection in Crohn’s disease strictures: a phase I-II, open-label clinical study
Authors: Vieujean S , Loly J P , Boutaffala L , Pariente B , Reenaers C , Briquet A , Lechanteur C , Beguin Y , Louis E
Published: May 2021

Background

Intestinal fibrosis is a common complication of Crohn’s disease (CD) leading to progressive bowel stricture formation. Mesenchymal stem cells (MSCs), known for their immunomodulatory, anti-inflammatory and anti-fibrotic properties, could be a potential therapy in this frequently fibro-inflammatory condition. In this phase I–II open-label pilot trial, we aimed to assess safety and efficacy of local MSCs injection in CD strictures.

Methods: CD patients with a non-passable stricture, length from 2 to 5 cm, accessible by ileocolonoscopy, but without intestinal obstruction, fistulas, or abscess, could be included. A total of 3X107 allogenic bone-marrow derived MSCs were equally injected in the 4 quadrants of the strictured bowel wall during an ileocolonoscopy. Adverse events and clinical scores (Crohn Disease Activity Index, Short Health Scale and Crohn Disease Obstructive Score) were evaluated at each follow-up visit (at week 4, 12, 24 and 48) while endoscopy was performed at baseline, W12 and W48. The main judgement criteria for efficacy was the complete (defined by the ability to pass the ileocolonoscope) or partial (defined by a diameter increase) resolution of the stricture at 12 weeks. Other efficacy criteria included complete or partial resolution of the stricture at 48 weeks as well as the evolution of clinical scores between weeks 0, 12 and 48.

Results

Between 2018 and 2020, we performed 11 local MSCs injections in 10 CD patients (6 female; aged to 38-65 years; median 45 years old; 70% were smoker). The strictures’ (3 primary, 7 anastomotic) location was as follows: 7 at an ileo-colonic or ileo-rectal anastomosis, 1 colonic and 2 of the ileocecal valve. MSCs injections were well tolerated but a total of 5 hospitalizations for occlusion were reported (2 secondary to a different stricture than the injected one) leading to a surgical resection for one patient and an endoscopic dilatation for another one. Neither intestinal perforation nor intra-abdominal fistula or abscess was reported. At 12 weeks, 5 patients (45%) presented a stricture improvement with a complete resolution for 2 and a partial resolution for 3. Of the 11 MSCs injections, 6 patients were re-evaluated at week 48 (2 patients still undergoing follow-up, 1 operated, 1 dilated, and 1 lost to follow-up), 4 patients had a complete resolution and 1 had a partial resolution. The evolution of clinical scores between weeks 0, 12 and 48 (Figure 1) was not statistically significant.

Conclusion

Local MSCs injection in non-passable CD stricture was well tolerated over the short term but several occlusions were reported in the follow-up. Combining the effects of MSCs with the proven effect of endoscopic balloon dilatation could possibly improve the outcome of CD stricture.
P344 Effectiveness and safety of switching patients with inflammatory bowel disease from originator infliximab to CT-P13: systematic review and meta-analysis
Authors: Hanzel J , Strik A , Gecse K , D’Haens G , Dreesen E
Published: May 2021

Background

Switching from originator infliximab (IFX) to the CT-P13 biosimilar is a widespread practice, although some concerns persist, particularly about long-term outcomes. We performed a systematic review and meta-analysis to assess the effectiveness and safety of switching from originator IFX to CT-P13 in patients with inflammatory bowel disease (IBD).

Methods

We systematically searched electronic databases for randomised controlled trials and prospective observational studies of adult patients with IBD who had switched from originator IFX to CT-P13 and were followed up for at least 12 months. The main outcomes were the pooled rate of clinical remission (as defined by the included studies) and adverse events at 12 months. Secondary outcomes included the rate of treatment discontinuation and de novo immunogenicity. A DerSimonian-Laird random-effects meta-analysis of proportions with double arcsine transformation was performed. Variables judged to be clinically important were studied in an exploratory random-effects meta-regression analysis.

Results

Eleven studies with 1204 patients (71% with Crohn’s disease [CD]) switching from originator IFX to CT-P13 were identified. Pooled rates of clinical remission at 12 months were 83.6% in ulcerative colitis (UC), 75.9% in CD, and 79.6% in mixed cohorts (Figure 1). Clinical remission at 12 months was negatively associated with combined immunosuppression at switch (7% decrease in remission at 12 months per 10% increase in patients receiving combination therapy) and positively associated with remission at switch (6% increase in remission at 12 months per 10% increase in remission at switch). The pooled rate of adverse events at 12 months was 21.0% (95% confidence interval [CI] 10.4–34.1%). Pooled rates of treatment discontinuation at 12 months were 24.4% (95% CI 12.0–39.4%) in UC, 18.6% (95% CI 8.8–30.9%) in CD, and 13.1% (95% CI 0.7–35.6%) in mixed cohorts. De novo immunogenicity was rare (3.3%, 95% CI 1.5–5.6%). All estimates had at least moderate heterogeneity.

Figure 1: Meta-analysis of clinical remission rates at 12 months after switching from originator infliximab to CT-P13 in ulcerative colitis and Crohn’s disease.

Conclusion

Switching from originator IFX to CT-P13 appears to be effective and safe, although these findings should be interpreted in the context of the limitations of the primary publications which lacked control arms. Combined immunosuppression at switch, potentially as a marker of disease severity, was negatively associated with clinical remission at 12 months after the switch.
P354 Early treatment versus active surveillance after ileocolic resection in Crohn’s disease: a retrospective cohort study
Authors: Haenen S , Sabino J , Bislenghi G , D’Hoore A , Ferrante M , Vermeire S
Published: May 2021

Background

Patients with Crohn’s disease (CD) often require ileocolic resection (ICR) due to refractory disease or disease-related complications, such as intestinal strictures, enteric fistulae or intra-abdominal abscesses. Up to 70% of patients will develop new endoscopic lesions in the neoterminal ileum within the first year after surgery. We assessed if the timing of postoperative treatment can reduce postoperative recurrence (POR) rate.

Methods

We performed a retrospective, single-center observational cohort study in a tertiary hospital. All CD patients undergoing abdominal surgery from January 1st 2015 until June 30th 2019 were screened. Patients with CD who underwent ileocolic resection with ileocolic anastomosis were included. Depending on the postoperative management patients were divided in two groups: “wait and see” if medical treatment was not initiated before endoscopic evaluation 6 months after surgery (n=109), “treat” if medical treatment was initiated directly after surgery (n=49). Patients whose postoperative follow-up occurred in another center were excluded. Data were collected by review of the electronic medical charts and included patient demographics, disease characteristics (Montreal classification), medication, indication for surgery and POR assessment. POR was defined as clinical (PRO2 pain >1 or loose stool frequency >1.5), endoscopic (Rutgeerts score > i2a) or radiologic (disease activity on MR enterography necessitating treatment). Survival analysis was performed with Kaplan-Meier and Cox proportional hazards model.

Results

In total 158 patients met the inclusion criteria: 109 patients in the “wait and see” group and 49 in the “treat” group. The main baseline characteristics of the cohorts are summarized in figure 1. The main indication for surgery was stricturing disease in both groups (69.7% and 65.3%) followed by penetrating disease (42.2% and 24.5%) and refractory disease (6.4% and 20.4%). Postoperative management did not significantly influence the risk for POR (figure 2). The same was also observed in patients with known risk factors for POR (figure 3). Patients with a high body mass index (>25 kg/m²) had a significant greater risk for developing POR (HR 1.65, CI 1.09-2.5, p=0.019; figure 4).

Conclusion

There was no statistical significant difference in POR between immediate treatment after ICR and active surveillance with endoscopy 6 months after surgery. Prospective randomized trials with long follow-up are needed to further explore the use of adjuvant postoperative treatment to prevent POR.
P384 Therapeutic drug monitoring: performance of the first lateral flow-based Point of Care test for the quantification of infliximab in a finger prick
Authors: Ametzazurra A , Pascual J , Del Rio L , Maguregui A , Nagore D , Ruiz-Argüello M B
Published: May 2021

Background

Promonitor Quick IFX is a lateral flow test (LFT) for the quantification of infliximab (IFX) in human whole blood (finger prick or venous) or serum in 20 minutes. This LFT is based on a sandwich immunoassay to quantify either the reference IFX or biosimilars. This abstract describes the studies performed to establish the analytical specifications of the product.

Methods

Clinical and Laboratory Standards Institute (CLSI) guidelines were followed for the evaluation of the analytical specifications of the LFT in whole blood and serum matrices: Linearity (EP-06-A), Detection capability (EP17-A2), Interfering substances (EP07, 3rd Edition), Intermediate precision (EP05-A3) and Bias evaluation study for Biosimilars (EP10-A3). Results were obtained in combination with the automated portable reader PQreader. A Datamatrix provided with each Promonitor Quick IFX kit contains the calibration information required for the PQreader to measure the Control and Test lines and report the IFX concentration.

Results

The linear assay range was determined to be 1-58 µg/mL in whole-blood and 0.6-67 µg/mL in serum according to the processes indicated in the Package Insert. The Limit of Blank is 0.8 μg/mL, the Limit of Detection and Lower Limit of Quantification (LLoQ) are 1.1 μg/mL, and the Upper Limit of Quantification (ULoQ) is 15.4 μg/mL.

There was no effect on assay performance when each of the following substances were added to samples with 0, 3, and 7 μg/mL of IFX: Haemoglobin (>1000 mg/dL), Bilirubin (>40 mg/dL), Triglycerides (>1500 mg/dL), HAMA (160 AU/mL), Rheumatoid factor (200 IU/mL), EDTA (5.4 mg/mL), Heparin (51 U/mL), Citrate (11.4%), Vedolizumab (60 μg/mL) and Adalimumab (20.25 μg/mL).

Repeatability and within-device precision results obtained for the positive samples are shown in the table below.

The negative samples showed a negative result in all the measurements.

A bias study showed that Promonitor Quick IFX can quantify CT-P13, SB2 and GP1111 biosimilars throughout the measurement range with a maximum bias of 14%.

Conclusion

Promonitor Quick IFX is the first LFT available for true Point of Care testing of patients treated with IFX with just a finger prick sample. It provides quick turnaround time to facilitate therapeutic drug monitoring and aid immediate decision making in the doctor office or hospitals with an excellent analytical performance.
P449 Cost Effectiveness of a Proactive Therapeutic Drug Monitoring Strategy in Patients with Inflammatory Bowel Disease Receiving Infliximab
Authors: Doherty J , Varley R , Healy M , Dunne C , Mac Carthy F , Mc Kiernan S , Hartery K , Kevans D
Published: May 2021

Background

Proactive therapeutic drug monitoring (TDM) has not demonstrated improved therapy outcomes compared with clinically-based dosing strategies. While the use of proactive TDM incurs additional assay-related costs this strategy may be cost-effective due to TDM-driven therapy dose de-escalation and discontinuation.

Methods

We aimed to assess if proactive-TDM is cost-effective in clinical practice. A proactive TDM strategy was utilized in our unit with infliximab (IFX) and antibody-to-infliximab (ATI) levels assessed at trough in all inflammatory bowel disease(IBD) patients receiving IFX. Baseline demographics and IFX dosing schedules were documented. Patients were grouped based on disease activity status. Patients with IFX levels outside therapeutic range had dosing adjusted as appropriate. IFX dose adjustments were not protocolized and were at physicians discretion. IFX dosing regimens following proactive TDM were documented and net effect on IFX infusions number over the subsequent year extrapolated. Increase or decrease in drug-related costs on an annualized basis were estimated.

Results

108 patients were included. Median age 36 years. 46% were female. 36% had ulcerative colitis, 60% Crohn’s disease. 35% were receiving concomitant immunomodulators. 56% were in remission at the time of TDM. 44%, 30% and 26% had IFX levels < 3 µg/mL, 3 – 7 µg/mL and > 7 µg/mL. IFX levels were significantly lower in patients with active disease compared with those in remission(p=0.008). Following proactive TDM assessment 37%, 11%, 36%, 13%, 2% and 1% of patients had no treatment change, therapy discontinuation, interval shortening, interval lengthening, dose increase and dose decrease respectively. Cost-effectiveness analysis focused on patients in remission (n=59). The use of proactive TDM-based IFX dosing resulted in a projected annualized reduction of 19.5 and 28.5 infusions due to IFX discontinuation and interval lengthening; the projected annualized increase in infusions was 39.1 and 4.3 due to IFX interval shortening and dose increase. This resulted in a net projected reduction of 4.7 IFX infusions per annum. Utilizing publicly available list prices for originator and biosimilar IFX and accounting for assay cost, projected cost savings resulting from proactive-TDM was 9105.0 and 6840.7 Euro per annum.

Conclusion

Proactive TDM in IBD patients in remission resulted in a modest reduction in the projected annualized number of infusions in our unit with consequent minor drug-related cost savings. Proactive-TDM encouraged cost-effective prescribing of IFX, however, the effect was minor. The frequency at which proactive TDM should be performed and whether subsequent rounds of proactive-TDM would continue to deliver similar cost savings is uncertain.
P463 COVID-19 vaccination willingness and hesitancy in patients with Inflammatory Bowel Diseases (IBD): analysis of determinants in a national survey of the Italian IBD patients’ association (AMICI Onlus)
Authors: Costantino A , Noviello D , Conforti F S , Aloi M , Armuzzi A , Bossa F , Ficari F , Leone S , Manguso F , Mocci G , Orlando A , Pironi L , Radice S , Rizzello F , Tongiorgi A , Costantino C , Vecchi M , Caprioli F
Published: May 2021

Background

Vaccine hesitancy, the delay in acceptance or refusal of vaccination despite its availability, represents a threat to the diffusion and lethality of infectious diseases. COVID-19 vaccination has been recommended by national and international organizations in patients with Inflammatory Bowel Diseases (IBD). The aim of the study was to evaluate COVID-19 vaccine willingness and hesitancy in a population of Italian patients with IBD, and their determinants.

Methods

In February 2021 an online questionnaire focused on COVID-19 vaccine was proposed to a representative sample of Italian IBD patients. Socio-demographic characteristics, IBD features, lifestyle, perception of COVID-19, general attitude towards vaccinations and to COVID-19 vaccines were investigated. Patients were divided into willing, hesitant and refusive towards COVID-19 vaccine. The hesitation reasons were investigated. The associations between baseline characteristics and willingness (determinants) were evaluated by calculating crude and adjusted Odds Ratio (AdjOR) with 95% confidence intervals (CI).

Results

The baseline characteristics are shown below. 1252 surveys were collected. 1005 (80.3%), 222 (18.1%) and 33 (2.63 %) patients were defined as willing, hesitant and refusive, respectively. Concerns for vaccine adverse effects constituted the main reason for refusal (73.4%) (Figure). 49.1% of hesitant patients reported that presence of IBD exerted an influence on their answer. Among the patients willing to be vaccinated whenever possible, 78.2% (786) thought that their IBD represented a valid motivation to access vaccination with priority. Willingness to COVID-19 vaccine was significantly associated with adherence to previous vaccinations (AdjOR 17.6, 95% CI 11.4–27.2), male gender (1.68 95% CI 1.16–2.43), graduation degree (1.48, 95% CI 1.03–2.13), perceived higher risk of COVID-19 due to IBD (1.47, 95% CI 1.05–2.08), alcohol intake (1.69, 95% CI 1.16–2.45). Conversely, the hesitancy was significantly associated with use of complementary and alternative medicines (0.58, 95% CI 0.36–0.92). Notably, 54.5% of patients were under the impression to have a higher risk of COVID-19 and 31.8% a more severe course due to their IBD.

Conclusion

Most IBD patients would accept COVID-19 vaccines, though one out of five is hesitant to date, principally due to fear of adverse events. The knowledge of determinants and reasons for COVID-19 vaccination acceptance could be a key element in developing targeted communication strategies to address vaccine hesitancy.
P470 Ustekinumab Trough Levels are not Associated with Clinical Response in Inflammatory Bowel Disease Patients
Authors: Zelinkova Z , Lipovska A , Otottova K , Lucenicova J , Kadleckova B
Published: May 2021

Background

Ustekinumab (UST) has been shown to effectively induce and maintain remission in inflammatory bowel disease (IBD). Only a few studies thus far have focused on UST pharmacokinetics suggesting that both, trough levels after i.v. induction as well as trough levels during stable maintenance might be associated with clinical and endoscopic response to UST. Data from real-world cohorts in this setting are scarce. Therefore, the aim of our study was to assess whether clinical response to UST was associated with a specific pharmacokinetic pattern.

Methods

All IBD patients treated with UST in one tertiary IBD centre between January 2017 and August 2020 were retrospectively retrieved from the database. Disease activity was assessed by Harvey-Bradshaw index (HBI) and partial Mayo score in Crohn’s disease (CD) and ulcerative colitis (UC) pts; respectively. Clinical response was defined as a decrease of HBI of ≥2 points or partial Mayo score ≥3 points. Patients not responding to therapy by week 16, or loosing original response received dose escalation from 90mg s.c. every 8 weeks to 90mg every 4 weeks. UST through levels were assessed by commercially available ELISA kit (IDKmonitor®) at week 8 after i.v. induction and/or during maintenance therapy after a minimum period of 16 weeks of treatment.

Results

In total, 61 IBD patients were included (mean age 38 years, range 22–70; 38 women; 54 CD/6 UC/1 IBD-U). All patients were antiTNF experienced, minority (11; 18%) had also been treated with vedolizumab prior UST. Thirty-nine pts (64%) were responders, out of these 15 pts (38%) required dose escalation at some point of the treatment due to secondary loss of response.

UST through levels at week 8 were significantly higher than the maintenance levels (mean 5.6±SEM 0.7µg/mL vs. 2.2±0.3µg/mL; p<0.001). There were no significant differences between responders and non-responders neither in trough levels after induction (5±0.8µg/mL vs. 6.4±1.1µg/mL, p=n.s.), nor in trough levels during maintenance therapy (2.3± 0.4µg/mL vs. 1.9 ±0.4µg/mL, p=n.s.). Patients requiring dose escalation did not differ from stable responders in maintenance trough levels (2.4±0,6 µg/mL vs. 2,3 ±0,4 µg/mL).

Conclusion

In this limited size real-world cohort of IBD patients, we found no difference in pharmacokinetics between reponders and non-reponders to ustekinumab.