bluuebunny/crossref_metadata_2025 huggingface dataset:
P299 Disability in newly diagnosed patients with Crohn′s Disease: initial results from the prospective CROCO (Crohn′s Disease Cohort) Study
Authors: Tinoco da Silva Torres J , Ellul P , Vieujean S , Ordas I , Burisch J , Mocanu I , Duricova D , Rodríguez-Lago I , Buisson A , Goldis A , Hernandez V , Arebi N , Kaimakliotis I , Nachury M , Fumery M , Allocca M , Pedersen N , Barberio B , Shaji S , Guedes A , Ribeiro R , Ungaro R , Lambert J , Colombel J F
Published: January 2023

Background

CD is classically seen as a progressive disease leading to bowel damage and disability. Disability has been proposed by the Spirit-IOIBD consensus1 as an endpoint in disease modification trials. However, there is a paucity of data regarding disability in CD patients at diagnosis.

Methods

The “Crohn′s Disease Cohort Study” (CROCO) is an ongoing prospective cohort aiming to study the longitudinal evolution of bowel damage and disability following diagnosis of CD. All patients are included within 12 months following CD diagnosis and will be followed over 5 years with serial assessments of bowel damage and disability. At recruitment patients completed an IBD disability score questionnaire (DS),2 comprising several domains: mobility, self-care, major daily life activities, gastrointestinal-related problems, mental health and interaction with the environment. We here describe the baseline DS and its association with disease features, disease activity score (Harvey-Bradshaw Index), and biomarkers of disease activity, on the first patients recruited into CROCO.

Results

Ninety-four patients were recruited, of which 66 filled at least 80% of the questions in the DS questionnaire; of those 55% were male and median age at diagnosis was 30.6 [IQR 24.2;38.8]. The baseline visit occurred at a median time of 6 months [IQR 2.6;9.2] after CD diagnosis. Ileal involvement (L1/L3) was reported in 82% of patients; 68% had B1 phenotype, and 26% presented extra-intestinal manifestations. Overall, 32% of patients had been hospitalised, and 6% had a history of CD-related surgery. Regarding medication [from diagnosis to baseline], 55% received steroids, 56% immunosuppressants, and 65% Anti-TNF therapy. The median DS was 79 [IQR 67;108.2] (range: 49;198); only 2 patients (3%) patients presented DS>162 (the central value of the DS), indicating no or mild disability. No correlations were found between clinical or analytical biomarkers of disease activity at the time of recruitment (Table 1). Associations between disease features and DS are displayed in Table 2. A history of CD-related hospitalisation was associated with a significantly higher DS (103 [IQR 79;157] versus 76.5 [65.5;97], p=0.013). No other associations were observed.

Conclusion

In a cohort of newly diagnosed CD patients, disability was mostly mild and independent of disease activity, disease location or behaviour; around 1/3 required hospitalisation within the first year of diagnosis, which was associated with increased disability. These data add to the growing concept that newly diagnosed disease represents a window of opportunity for intervention.
P315 The characteristics and severity of pediatric ulcerative proctitis
Authors: Müller K , Dohos D , Imrei M , Gombos E , Szentannay J , Szabó A , Oberfrank M , Karoliny A
Published: January 2023

Background

The diagnosis of ulcerative proctitis is rarer in childhood than in adulthood (4-29% vs. 44-60%). According to the literature, the prognosis of ulcerative colitis is favourable, however one third of the patients require biological therapy during follow-up, and the localization may extend in 20-25% in 5 years. Our aim was to compare the disease characteristics at diagnosis in children with ulcerative proctitis and with more extensive ulcerative colitis.

Methods

Retrospective, single centre analyses of patients with ulcerative colitis, diagnosed between 2010-2022 at the Heim Pál National Paediatric Institute, Budapest, Hungary. We compared the initial demographic, anthropometric data, and laboratory parameters of children with ulcerative proctitis (E1) and more extensive ulcerative colitis (E2-E4) according to the Paris classification. The analyses were performed with descriptive statistics and 2 samples t-tests.

Results

Between 2010-2022, of the 127 children were diagnosed with ulcerative colitis, 22 had proctitis (17.3%; 10 male; mean age: 15.0±1.9 year) and 105 had more extensive disease (82.7%; 53 boy; mean age: 12.2±3.8 year). The mean age was significantly higher in the proctitis group. The initial CRP, platelet count and faecal calprotectin (FCP) level was significantly lower (CRP [mg/l]: 1.2±1.4 vs. 12.0±21.5, p<0.001; thrombocyte [G/l]: 264.9±611.9 vs. 420.6±183.7, p<0.001; FCP [μg/mg]: 416.5±411.4 vs. 1054.5±316.6, p=0.001); while the haematocrit and albumin level was significantly higher (haematocrit [%]: 38.6±3.1 vs. 33.6±5.2, p<0.001; albumin [g/l]: 46.6±2.9 vs. 42.7±4.4, p<0.001) in the proctitis group compared to the other group. BMI z-score value at diagnosis was significantly higher in the proctitis group (0.45±1.4 vs. -0.12±1.2, p=0.02). The initial activity index (PUCAI) was significantly higher in the more extensive group (at diagnosis: 25.0±11.0 vs. 45.1±18.9, p<0.01).

Conclusion

Our results are in line with the literature, that the proportion of ulcerative proctitis is low in children. Based on our results, the manifestation of ulcerative proctitis presents in a milder form than more extensive colitis. Though it is important, that physicians should always consider the extension of the disease and need for treatment escalation to reach mucosal healing.
P319 Characteristics of filgotinib-treated patients with Ulcerative Colitis who achieve sustained corticosteroid-free remission: Post hoc analysis of the phase 2b/3 SELECTION study
Authors: Kobayashi T , Dignass A , Roblin X , Fujitani Y , Oortwijn A , Jamoul C , Hibi T
Published: January 2023

Background

Filgotinib (FIL) is a once-daily, oral, Janus kinase 1 preferential inhibitor approved for the treatment of ulcerative colitis (UC) in Europe and Japan. The efficacy and safety of FIL in patients with moderately to severely active UC was evaluated in the phase 2b/3 randomized, double-blind, placebo (PBO)-controlled SELECTION study (NCT02914522).1 This post hoc analysis aimed to identify characteristics of FIL-treated patients that were associated with achieving corticosteroid (CS)-free remission.

Methods

Adults aged 18–75 years were randomized 2:2:1 to induction FIL 100 mg, FIL 200 mg or PBO once daily for 11 weeks in induction study A (biologic-naive) and B (biologic-experienced). At week 10, patients in clinical remission or with a Mayo Clinic Score (MCS) response were re-randomized 2:1 to continue their FIL regimen or PBO for 47 weeks in the maintenance study. This analysis included only data from patients receiving CSs at baseline. Using univariate logistic regression, we analysed characteristics associated with achieving clinical remission at week 58 without using CSs for UC over a continuous period of ≥6 months (CS-free remission). P values <0.05 were considered statistically significant.

Results

At baseline, 81, 37, 92 and 47 patients were receiving CSs in the maintenance FIL 100 mg (n=172), PBO-to-match (PTM) FIL 100 mg (n=89), FIL 200 mg (n=199) and PTM FIL 200 mg (n=98) groups, respectively. The rates of CS-free remission in the FIL 100 mg, PTM FIL 100 mg, FIL 200 mg and PTM FIL 200 mg groups were 13.6%, 5.4%, 27.2% and 6.4%, respectively. Age, body mass index, history of pancolitis, duration of UC, faecal calprotectin and C-reactive protein levels, MCS and concomitant use of systemic CSs, immunomodulators and aminosalicylates had no significant effect on CS-free remission in the FIL 200 mg group. Mean baseline Robarts Histopathology Index (RHI) (odds ratio [OR]=0.949, p=0.023) was significantly associated with 6-month CS-free remission in the FIL 200 mg group. A baseline Mayo endoscopic subscore (MES) of 2 (vs 3) was associated with significantly increased odds of 6-month CS-free remission in the FIL 200 mg and FIL 100 mg groups (Table). Being male, a former (vs current) smoker or biologic-experienced was associated with significantly reduced odds of 6-month CS-free remission in the FIL 200 mg group.

Conclusion

Most baseline characteristics analysed had no statistically significant effect on 6-month CS-free remission under FIL 200 mg treatment. Low baseline MES and RHI, female sex, being a current (vs former) smoker and biologic-naive may predict higher likelihood of sustained CS-free remission in patients receiving FIL 200 mg.
P326 PREFAB-study: PRediction tool for Early identification of patients at risk of Crohn's disease in perianal Fistulas and ABscesses: interim analysis of a prospective pilot study at a non-academic, IBD-expert centre in the Netherlands
Authors: Munster L , de Groof E J , van Dieren S , Mundt M W , D’Haens G R A M , Bemelman W A , Buskens C J , van der Bilt J D W
Published: January 2023

Background

Perianal abscesses (PAA) and perianal fistulas (PAF) are life impairing conditions associated with Crohn’s disease (CD). A retrospective study at Flevohospital showed a reduced median delay in diagnosis of CD from 33 months (IQR 23-64) in the period 2007-2016 to 3 months (IQR 0-5) in the period 2017-2021, with <20% of patients diagnosed <1 year after the first perianal surgical procedure in 2007-2016 versus 79% in 2017-2021. This study also showed CD in up to 10% of patients with PAA/PAF, which was reason to continue data collection in a larger prospective pilot study to identify risk factors for CD in patients presenting with PAA/PAF.

Methods

All consecutive patients ≥16 years presenting with PAA/PAF were included. Patients were prospectively screened for risk factors/red flags from a ‘perianal Red Flag Index Questionnaire’ (pRFI) (identified from previous literature searches/expert opinion) and fecal calprotectin (FC-)samples were taken in all patients. Colonoscopy was performed in case of ≥5 positive answers in the pRFI and/or FC-values ≥150mcg/g.

Results

Sixty-nine patients were included (72,5% male) with median age of 41 years (IQR 30,5-54,6). Thirty-five patients (50,7%) presented with PAA, whereas 34 patients presented with PAF (49,3%). Thirty-one patients (44,9%) had recurrent PAA/PAF. Additional colonoscopy was performed in 11 patients, in whom 5 patients (7,2%) eventually were diagnosed with CD with a median delay of 44 months (IQR 7,5-87,5, still 5 patients in diagnostic work-up). Median FC-values were 552mcg/g (IQR 198,5-4585) in patients with confirmed CD and 31,5mcg/g (IQR 10-102,75) in patients without CD (p=0,002). Risk factors associated with CD were a younger age, presence of PAF (compared to PAA only), higher number of previous perianal interventions, multiple internal fistula openings, fissures and proctitis (p<0,05 in all).

Conclusion

This pilot study reveals several risk factors associated with CD in patients presenting with PAA/PAF and forms the basis for development of a clinical decision tool that incorporates both the pRFI questionnaire and selected FC-measurement to early identify patients at risk of CD when presenting with perianal disease. This clinical decision tool will be subject of a larger prospective multicentre study to reduce diagnostic/treatment delay, thereby improving outcomes in patients with Crohn’s fistulas.
P331 Risk Factors and Prediction Model for Fecal Incontinence in Patients with Crohn’s Disease: A Multicenter Study
Authors: Wang C , Yang F , Qiao L , Chen Q , Chen H , Li Y , Zhang X , Liao X , Cao L , Xu H , Xiang Y , Wang X , Yang B ,   Department of Colorectal Surgery Affiliated Hospital of Nanjing University of Chinese Medicine Jiangsu Province Hospital of Chinese Medicine Nanjing China
Published: January 2023

Background

Fecal incontinence (FI) is a common complaint that seriously affects the quality of life in patients with Crohn’s disease (CD). We aimed to identify risk factors related to FI and construct a risk prediction model for FI in patients with CD.

Methods

Four hundred and sixty-one patients diagnosed with CD between June 2016 and April 2021 in Jiangsu Province Hospital of Chinese Medicine were retrospectively enrolled in this study and randomly divided into the development (n=368) and internal validation cohort (n=93). FI-related risk factors were selected from the development cohort using the random forest procedure and included in a logistic regression model from which the prediction model was elaborated. The discrimination, calibration and clinical benefit of the model were evaluated by examining the area under the receiver operating characteristic curves, calibration curves and decision curve analysis in internal validation and external validation (using 225 patients from four tertiary hospitals), respectively.

Results

Four independent variables were selected and included in the logistic regression model: body mass index, history of non-fistulizing perianal lesions surgery, the number of loose stools in the last week and perianal disease activity index. A nomogram was developed to facilitate risk score calculation. The model showed good discrimination ability with AUC was 0.798 and 0.780 in the internal and external cohorts, respectively. The calibration curves demonstrated good agreement with the model using the Hosmer-Lemeshow test in both cohorts (internal validation, P = 0.562; external validation, P = 0.383). DCA confirmed the clinical validity of the predictive model.

Conclusion

This study recognized four risk factors related to the prevalence of FI and developed a new model to effectively predict risk scores of FI in CD patients, helping to provide early risk stratification and timely intervention.
P333 Early intestinal ultrasound remission is associated with endoscopic healing after one year of infliximab therapy in Crohn’s disease: a multicentre prospective study
Authors: Revés J , Morão B , Nascimento C , Frias-Gomes C , Cúrdia Gonçalves T , Freitas M , Castro F , Moreira M J , Cotter J , Pereira F , Caldeira A , Sousa R , Coelho R , Macedo G , Glória L , Torres J , Palmela C
Published: January 2023

Background

Endoscopic healing (EH) is currently the consensual long-term treatment target to achieve in Crohn’s disease (CD). However, optimization of therapy based on an endoscopic response implies a delay as endoscopy is an invasive procedure and cannot be used longitudinally, stressing the need for non-invasive predictors of EH. We aimed to assess the predictive role of biomarkers and intestinal ultrasound (IUS) parameters after induction therapy to predict EH one year after infliximab (IFX) therapy.

Methods

Prospective multicentre cohort study including patients with active CD starting IFX. Harvey-Bradshaw index (HBI), C-reactive protein (CRP), faecal calprotectin (FC), and IUS were performed at week (W) 0, 14, 30, and 54. Ileocolonoscopy was performed at W0 and W54. Clinical remission (CR) was defined as HBI<5 and laboratory remission (LR) as CRP <0.5mg/dL and FC <150ug/g. Transmural healing (TH) was defined as the normalization of bowel wall thickness (BWT≤3mm), doppler sign (≤1), wall stratification, and inflammatory fat in the most affected segment. The IBUS-SAS (International Bowel Ultrasound Segmental Activity Score) was used to assess disease activity and includes BWT, doppler sign, loss of stratification, and inflammatory fat. EH was defined as total SES-CD <3.

Results

We included 52 patients with CD (54% male; mean age 35±14y). Baseline characteristics are available in Table 1. At W14, 89% were in CR, 46% had LR and 19% had TH. After 1 year of IFX therapy, 90% were in CR, 62% had LR, 43% had TH and 37% had EH. At W14, patients with EH had lower BWT (3.3 vs 4.6mm, p=0.01), lower IBUS-SAS (15 vs 61, p<0.01), and lower FC (44 vs 239ug/g, p<0.01). At W14, both TH (OR 11.3, 95%CI 2.1-61.4, p<0.01) and FC remission (OR 7.4, 95%CI 1.8-30.7, p<0.01) were significant predictors for EH. In a multivariate analysis including significant baseline characteristics and early non-invasive monitoring targets at W14 (table 2), TH was an independent predictor of EH (OR 8.6, 95%CI 1.2-61.7, p=0.03). Even after adjusting for the baseline ultrasonographic severity according to the IBUS-SAS, TH at W14 remained a significant predictor of EH (OR 6.5, 95%CI 1.02-40.9, p=0.047). Using a ROC curves analysis, the IBUS-SAS at W14 was the best predictor for EH, with an AUC of 0.81 and the best cut-off value of 32.2 (Table 3).

Conclusion

Early assessment of ultrasonographic remission at week 14 can help predict EH after one year of therapy and offers an opportunity for early therapy optimization. TH at week 14 assessed by IUS was an independent predictor for EH after one year of therapy. Our results support the use of early IUS monitoring to predict response to therapy in CD patients.
P336 Endoscopic scores as predictors of treatment failure in Ulcerative Colitis
Authors: Ferreira A I , Lima Capela T , Xavier S , Arieira C , Cúrdia Gonçalves T , Dias de Castro F , Moreira M J , Cotter J
Published: January 2023

Background

The endoscopic Mayo score (MS) is the most frequent score used for the evaluation of inflammatory activity in Ulcerative Colitis (UC), varying from 0 to 3 points. Recently the DUBLIN score (DS) emerged, which varies from 0 to 9 points and results from the product of the MS and the disease extent, according to Montreal classification, E1-E3. In this study we aimed to evaluate and compare the predictive ability of MS and DS for long term treatment failure.

Methods

A retrospective and unicentric study was conducted, including patients with left-sided or extensive UC, asymptomatic and without the need for steroid therapy or therapy changes in the 6 months prior to undergoing total colonoscopy with calculation of MS and DS. Treatment failure was evaluated, defined by the need for therapy changes and/or hospitalization because of disease exacerbation, over a follow-up period of a minimum of 24 months and a maximum of 84 months.

Results

A total of 204 patients were included, 104 (51%) females and with a mean age at diagnosis of 36.4±12.7 years. In the initial evaluation, 48 (23.5%) were being treated with anti-TNFα medication. The mean values of MS were 1.0±1.1 points and of DS were 2.2±2.6 points. During follow-up, 32 (15.7%) patients experienced treatment failure and patients initially treated with anti-TNFα medication had 2.3 times higher risk of treatment failure (p=0.042). MS values (AUC 0.809; p<0.001; with sensitivity of 0.938 and specificity of 0.529 for values equal or superior to 1) and DS values (AUC 0.789; p<0.001; with sensitivity of 0.844 and specificity of 0.581 for values equal or superior to 2) had good discriminative abilities in predicting treatment failure. There were no statistically significant differences in the discriminative ability between both scores (p=0.340).

Conclusion

MS and DS had good discriminative abilities in predicting treatment failure. However, the integration of the disease extent in the DS as a complement of MS in the evaluation of UC was not associated with a higher predictive ability of long term treatment failure.
P337 Developing Preliminary MRI-based Classifier for Perianal Fistulizing Crohn’s Disease by Using Deep Convolutional Neural Networks
Authors: Zhang H , Li L , Deng K , Li W , Ren D
Published: January 2023

Background

Early diagnosis and management of perianal fistulizing Crohn’s disease (PFCD) is critical. But there is still lack of single reliable diagnostic modality to differentiate between early PFCD and cryptoglandular anal fistula (CAF). This study aimed to evaluate the feasibility and efficacy of deep convolutional neural networks (DCNNs) for distinguishing PFCD from CAF based on pelvic magnetic resonance imaging (MRI).

Methods

The MRIs from 400 patients primarily diagnosed with PFCD or CAF (two hundred respectively) were retrospectively collected as datasets and used in this study. All patients had no fistula associated surgical histories. The datasets were split into training (80%), validation (10%), and test(10%). Four different DCNNs, MobileNetV2, VGG11, ResNet18 and ResNet34, were trained to classify the patients with fistula MRIs as PFCD or as CAF. Both untrained and pretrained networks were used. Pretrained networks were obtained from the Pytorch Models, an open-access repository of pretrained models for use with Pytorch. The protocol was shown in Figure 1 and was approved by the institutional review board (2022ZSLYEC-421).On the test dataset, receiver operating characteristic curves and areas under the curve (AUCs) were used to assess model performances and were compared with the performances of radiologists. Comparisons between AUCs were made by using the Delong method. Accuracy, sensitivity, and specificity were determined from the optimal threshold by the Youden index.

Figure 1.

Results

Compared with CAF, the PFCD dataset contained more high fistulas (59.5% vs. 44.5%，P=0.003), more fistulas involved in the deep anterior space (15.5% vs. 3.0%，P<0.001), and less abscess formation (32.5% vs. 59.5%，P<0.001). Other fistula characteristics including ramification formation, supra- or infralevator extension, were not statistically different. The performances of the pretrained models were better than that of the untrained models (Figure 2). The AUC of 4 pretrained DCNN classifiers were MobileNetV2 [AUC: 0.943，95%CI（0.820~0.991）], VGG11 [AUC: 0.935, 95%CI（0.810~0.988）], ResNet 18 [AUC: 0.920, 95%CI（0.789~0.982）], ResNet 34[AUC: 0.929, 95%CI（0.801~0.986）] respectively. The performances of 4 pretrained DCNN classifiers were equivalent to that of senior radiologist, and were superior to that of junior radiologist (Figure 2, 3, 4).

Figure 2.

Figure 3.

Figure 4.

Conclusion

Deep learning with DCNN in classifying PFCD or CAF on perianal MRI is feasible. Transfer learning may further improve the performance of the DCNN model. A larger sample size dataset to train the former DCCNs is conducting in our constitution and the external validation will be added in the future.
P348 Disease trajectories in ulcerative colitis: Early identification of patients with endoscopic remission at Week 52
Authors: Schreiber S W , Danese S , Dirk L , Agboton C , Colombel J F
Published: January 2023

Background

Clinical understanding of different disease courses in response to targeted therapies in ulcerative colitis (UC) is lacking. Symptom load over time can help to define different trajectories leading to outcome measures at week 52. This post hoc analysis from the GEMINI 1 study of vedolizumab (VDZ) vs placebo for the treatment of moderately to severely active UC1 aimed to define different clinical patterns of response that led to Week 52 endoscopic remission based on daily collection of symptom data: rectal bleeding (RB) and stool frequency (SF).

Methods

RB and SF data, each scored 0 to 3, were extracted from the diary cards of patients who were treated with VDZ up to Week 50, had clinical outcome assessed at Week 52 and had sufficient diary data. From the daily scores, six different daily symptom score rules comprising RB alone or various combinations of RB and SF (Table 1) were derived. Each of the six symptom score rules was then accrued over the time to derive cumulative symptom scores (area under the curve [AUC]). The AUCs at Weeks 6, 10, 14 and 22 for each rule were evaluated for sensitivity and specificity to predict endoscopic remission at Week 52, which was defined as Mayo endoscopic subscore of ≤1 point.

Results

Of the 895 pts included in the GEMINI 1 study, 217 pts were treated with VDZ, had sufficient RB and SF data and Week 52 outcome data. Of these, 157 (72.4%) achieved endoscopic remission at Week 52. Rule 4, with a score of 0 if both RB=0 and SF≤1 or 1 if not, was consistently better at predicting response at Week 52, i.e., had largest area under the receiver-operator characteristic (ROC) curve (Week 10 and Week 14 shown in Table 2). Area under ROC curve for Rule 4 was 0.7317 (0.6578, 0.8057) and 0.7534 (0.6810, 0.8258) at Week 10 and Week 14, respectively (Fig 1). Rule 4 had better predictive performance than the use of RB Mayo score (RB1) alone or the simple dichotomization (RB2, 0 if RB≤1, 1 if RB >1) [Table 2]. AUCs for Rule 4 differed between pts with vs without endoscopic remission at Week 52, with differences evident as early as Week 10: median AUC=41 for pts with endoscopic remission vs 70 for pts without (Fig 2).

Conclusion

The daily collection of RB and SF symptoms during the first weeks of therapy with VDZ identifies patients with a high likelihood for endoscopic emission at Week 52. Early clinical symptom change is a simple method for tight monitoring of patients with UC. The identification of preferential responder populations in which marked reduction of suffering are combined with hard endpoints could help in establishing treatment optimization algorithms for targeted therapies.

References:

1. Feagan BG et al. (2013) N Engl J Med 369:699–710
P349 Faecal Calprotectin in Ulcerative Colitis - Associations with Mucosal Inflammatory Activity and Disease Extent
Authors: Steinsbø Ø , Aasprong O G , Karlsen L N , Aabakken L , Grimstad T
Published: January 2023

Background

In ulcerative colitis (UC), faecal calprotectin (FC) correlates with endoscopic severity and disease extent, and low levels are associated with histological remission [1, 2]. The effect of mucosal inflammatory activity versus disease extent on the FC levels, remains poorly understood.

We aimed to compare FC levels in patients grouped by endoscopic and histologic scores of the inflammatory activity. We also grouped patients according to active disease extent based on endoscopic or histological evaluations.

Methods

This was a post hoc analysis of patients diagnosed with UC or with confirmed UC at Stavanger University Hospital, Norway, from 2012 to 2020. Visits were performed at diagnosis, and after 3 and 11 months. FC was analysed in samples collected from 4 weeks before until 3 days after visits (EliA Calprotectin or EliA Calprotectin 2, Thermo Scientific). At each visit, colonoscopy was performed, and biopsies were collected from three colorectal segments (rectum, left colon, right colon).

Mucosal inflammatory activity was scored endoscopically by Mayo Endoscopic Score (MES 0 – 3) and histologically by Nancy Histological Index (NHI 0 – 4). The highest value of the segmental NHI scores were reported.

Disease extent was defined by Montreal classification. Distribution of acute inflammation was defined by the number of colorectal segments with NHI ≥ 2 (presence of neutrophilic infiltrates).

Results

In total 554 visits of 249 patients were analysed. FC levels increased significantly for every stepwise increase in MES, and median FC was 30-fold (range 19-49) higher in MES 3 than in MES 0 subgroups. The largest difference was observed between MES 1 and MES 2 (Figure 1a).

FC levels also increased significantly for every stepwise increase in NHI, except between NHI 3 and NHI 4. Median FC level was 54-fold higher in NHI 4 group compared with the NHI 0 group, and the largest difference was observed between NHI 1 and NHI 2 (Figure 1b).

Disease extent showed little effect on FC, and significant difference was only observed between proctitis and pancolitis with 3-fold (range 1.6 – 4.5) higher levels in the latter groups (Figure 2a).

Median FC level was 3-fold higher in patients with acute inflammation in all 3 segments compared to patients with acute inflammation in only 1 colorectal segment (Figure 2b).

Conclusion

FC increased significantly by increasing mucosal inflammatory activity, whereas disease extent showed a modest effect on the FC levels. FC is an accurate and useful biomarker of both endoscopic and histological inflammatory activity in patients with ulcerative colitis.

References:

1. Kawashima K. et al, BMC Gasteroenterology 2016

2. Magro F. et al, Gut 2019
P362 Systematic review: Oncological outcomes of patients with Inflammatory Bowel Disease undergoing segmental colonic resections for colorectal cancer and dysplasia
Authors: Shamsiddinova A , Deputy M , Worley G , Rao C , Dean H , Thomas-Gibson S , Faiz O
Published: January 2023

Background

Current international guidelines recommend that patients with inflammatory bowel disease (IBD) diagnosed with high grade dysplasia (HGD), or colorectal cancer undergo a proctocolectomy, and that proctocolectomy is considered within a shared decision-making framework with the patient in cases of low grade (LGD) or indeterminate (IND) dysplasia. However, segmental colectomy (surgical resection leaving remaining colon or rectum) is considered by some as a valid alternative, with less physiological stress, stoma avoidance and thus acceptability to patients. This systematic review aims to assess oncological and post-operative outcomes in studies reporting on segmental colectomy or proctocolectomy for patients with IBD and colonic or rectal dysplasia and cancer.

Methods

This systematic review was prospectively registered with PROSPERO (CRD42021292891) and carried out in line with the PRISMA guidelines. Studies published between 1990 and 2022 reporting on oncological and surgical outcomes of adult patients undergoing segmental resection and/or proctocolectomy that included at least three cases of neoplasia were included. Descriptive statistics were used in the context of significant heterogeneity. A meta-analysis was performed for outcomes with at least three results.

Results

The search returned 2178 results, and after screening 12 studies were included in the final analysis. A total 12,701 patients were included reporting on outcomes of 10,386 segmental resections and 2,315 proctocolectomies. The pooled incidence of missed synchronous cancers (i.e. identified in remaining colon or rectum within 6 months of surgery) in the segmental resection group was 1.4%, and dysplasia 0.5%; metachronous cancer recurrence was 1.4% (1.1% in subtotal colectomy, 11.8% in any other segmental resection), and dysplasia recurrence 5.3% (4.7% in subtotal colectomy, 7.5% in any other segmental). Average time to recurrence for metachronous cancer was 6.5 years. Recurrence of metastatic cancer was 0.2% for proctocolectomy, and 0.1% for segmental resection (OR 1.28, 95% CI 0.19 - 8.65, p =ns).

Conclusion

Segmental colectomy does not disadvantage against metastatic cancer recurrence. The incidence of missed synchronous lesions is low. There is increased metachronous cancer risk, however this is mitigated by subtotal colectomy. These results may help to counsel patients regarding the risks and benefits of segmental resection for IBD-related dysplasia and cancer. The risk of metachronous cancer after segmental resection reiterates the need for enhanced high quality post-operative surveillance. The paucity of data in this field is also demonstrated here by the high inter-study heterogeneity, highlighting the need for prospective studies.
P368 The presence of extra-intestinal manifestations is associated with poor prognosis in acute severe ulcerative colitis: A KASID multicenter study
Authors: Kim D H , Kim E S , Kim H S , Park S H , Kim S J , Kim K O , Lee Y J , Song E M , Kim D S , Lee J ,   IBD Research Group in Korean Association for the Study of the Intestinal Diseases (KASID)
Published: January 2023

Background

Many patients with inflammatory bowel disease experience extra-intestinal manifestations (EIM)s. The presence of EIMs is related to disease activity. Acute severe ulcerative colitis (ASUC) is associated with a high inflammatory burden. However, there are insufficient studies on the relation between the presence of EIMs and the prognosis of exacerbation of ulcerative colitis. This study was conducted to elucidate the correlation between EIMs and ASUC.

Methods

We retrospectively included patients who were hospitalized at four tertiary medical centers for ASUC management between January 2015 to December 2020, and data on the underlying disease, disease activity, EIMs, colectomy, treatment method, and readmission due to ulcerative colitis aggravation were checked.

Results

A total of 145 patients (mean age 44.4 years, 68 women) were investigated. The initial partial Mayo score, the Mayo endoscopy sub-score, and the ulcerative colitis endoscopic severity index were 7.6±0.8%, 2.7±0.5, and 6.0±1.4%, respectively.

EIMs were expressed in a total of 10.3% (15/145) of patients. The most common type of EIMs was the peripheral articular type (46.7%) followed by skin lesions (20%) and axial articular disease (13.3%). The group with EIMs was younger and had a higher proportion of women than the group without EIMs (39.4 versus 45 years, p=0.03), and had a longer duration of disease (5.8 versus 3.5 years, p=0.02). The Mayo endoscopic sub-score (2.9 vs. 2.7, p<0.01) and partial endoscopic score (7.9 vs. 7.6, p<0.01) were also higher in the EIMs group. The length of hospital stay was also longer in the EIMs group (25.5 days vs. 13.8 days, p<0.01).

The response rate to initial treatment was lower in the EIMs group (71.4% vs. 95.5%, p<0.01), and more rescue therapy (28.6% vs. 4.5%, p<0.01) was performed. The rate of colectomy on admission was also higher in the group with EIMs (13.3% vs. 0.8%, p<0.01). Patients with EIMs showed a high tendency to visit the hospital for re-exacerbation of ulcerative colitis after discharge (p=0.07, HR 2.10 CI: 0.93 – 4.76).

Conclusion

EIMs were expressed in a total of 10.3% of patients with ASUC. The presence of EIMs suggested a poor prognosis in ASUC.
P369 Do teenager and adult onset Crohn′s disease patients have different outcomes? A Portuguese cohort study
Authors: Cerqueira R , Correia M , Veloso R , Manso M C
Published: January 2023

Background

Crohn’s disease (CD) is a chronic illness that, according to the age of onset, has disease heterogeneity. Comparing with CD adult-onset (AO), the teenager-onset (TO) may lead to a deeper health impact: late pubertal development and psychosocial problems. There is paucity of data comparing TO with AO in the biologics era.

The aim of this single center study was to compare disease characteristics, the use rate and predictive risk factors at diagnosis for CD biologic therapy (anti-TNF) and the rate of CD related surgery

Methods

Observational study designed as an analysis of a historical cohort: 298 CD patients followed up to 21 years (2000-2021), 49 TO (<20 years-old) and 249 AO (≥20 years-old). Median follow-up was 9 years in TO and 10 years in AO cohort (p=0.792).

The data collected included sex, and at diagnosis, age, smoking habits, CD location, CD behaviour, presence of perianal disease and extra intestinal manifestations. The independent effect of significant variables (p<0.05) was assessed using multivariate logistics regression analysis. The cumulative use rate of biologic therapy and CD related surgery were estimated using Kaplan-Meier plots.

Results

The TO cohort comprised 49 (16.4%) and the AO 249 (83.6%) CD patients. Upper digestive tract involvement and inflammatory behaviour at diagnosis were significantly higher in the TO cohort (p<0.001). Biologic therapy rate was significantly higher in TO than in AO (63.3% vs 43.8%, OR=2.21(95%CI:1.17-4.15), although the time span from diagnosis to the fist biologic use is independent of group (Log-Rank(Mantel-Cox);p=0.812). On multivariate analysis, predictive risk factors at diagnosis for biologic therapy in AO cohort were non-inflammatory phenotype, OR=2.75(95%CI:1.58-4.81), steroid therapy, OR=3.64(95%CI:2.05-6.47) and perianal disease, OR=14.49(95%CI:5.50-38.17); no significant predictive risk factors were identified in the TO cohort. Regarding CD related surgery, there was no significant different rates between the two age groups (18.4% in teens vs 26.1% in adults, OR=0.66(95%CI:0.31-1.45); p=0.300) and the time span from diagnosis to surgery was also independent of group (Log Rank(Mantel-Cox);p=0.204).

Conclusion

Compared with AO, TO CD has different characteristics and, «per se», is a higher risk for biologics drugs treatment.

However, TO CD is not associated with higher risk of surgery.
P370 Correlation of the IBD Disk with intestinal ultrasound in patients with inflammatory bowel disease
Authors: Katsaros M , Kalogirou M , Katsoula A , Paschos P , Karabatsou S , Tsionis T , Soufleris K , Giouleme O
Published: January 2023

Background

The Inflammatory Bowel Disease (IBD) Disk represents a self-administered questionnaire that can facilitate, in real time, assessment of IBD related disability, and IBD-related daily life burden. Surrogate markers of IBD activity tend to associate with increased disability. Intestinal ultrasound (IUS) is a non-invasive tool that can objectively and accurately define disease activity and complications in IBD patients. We investigated the correlation between IBD-Disk and IUS in IBD patients.

Methods

We performed a cross-sectional study that included formally diagnosed IBD patients who underwent IUS and subsequently completed the IBD-Disk questionnaire. Active disease on IUS was defined as bowel wall thickness (BWT) >3 mm at the most affected bowel segment. The overall IBD-Disk score was calculated as the sum of its 10 components, ranging from 0 to 100 (best score: 0, worst score: 100). We explored the correlation between IBD-Disk and its components with IUS. We additionally investigated the correlation of IBD-related daily life burden with IUS. (IBD-Disk total score > 40: high IBD related daily life burden vs IBD-Disk total score ≤ 40: low IBD related daily life burden).

Results

We included 49 patients (table 1), who underwent IUS for disease monitoring (59.2%) and symptoms suggestive of disease flare (40.8%). Median IBD-Disk total score in our cohort was 48 (IQR 18-58). Median IBD-Disk total score was 52 (IQR 47.3-61.5) in IUS active vs 16 (IQR 5-25) in IUS inactive patients (p<0.001). The area under the ROC curve of IBD-Disk total score in predicting IUS activity was 0.88 (95% C.I: 0.77-0.99, p<0.001, Figure 1). IBD-Disk score >31 predicted disease activity in IUS with 90.6% sensitivity and 88.2% specificity. We observed a moderate correlation between IBD-Disk score and BWT (ρ=0.61, p<0.001) as well as between IBD-Disk score and C-reactive protein (ρ=0.66, p<0.001). Among the components of the IBD-Disk, 8/10 manifested a moderate correlation with BWT (table 2). IBD-Disk score > 40 was found in 27/32 (84.4%) of IUS active and 2/17 (11.8%) of IUS inactive patients, while IBD-Disk score ≤ 40 was found in 5/32 (15.6%) of IUS active and 15/17 (88.2%) of IUS inactive patients respectively (p<0.001). Median BWT was 1.95 mm (IQR 1.53-4.40) in patients with IBD-Disk score ≤ 40 and 5.9 mm (IQR 4.8-6.8) in patients with IBD-Disk score > 40 (p<0.001).

Conclusion

IBD-Disk displayed a significant correlation with IUS evidence of disease activity in IBD patients. Active disease in IUS was significantly correlated with a high IBD-related daily life burden as expressed by IBD-Disk total score > 40. IBD-Disk could be used in clinical practice to evaluate disease activity and severity in IBD patients.
P374 Therapeutic drug monitoring can guide the intravenous-to-subcutaneous switch of infliximab and vedolizumab: a pharmacokinetic simulation study
Authors: Wang Z , Verstockt B , Sabino J , Ferrante M , Vermeire S , Dreesen E
Published: January 2023

Background

Subcutaneous (SC) formulations of infliximab (IFX) and vedolizumab (VDZ) were recently approved for maintenance treatment of patients with inflammatory bowel disease. However, further investigation is required to identify the patients most likely to benefit from intravenous (IV)-to-SC switch. We hypothesise that therapeutic drug monitoring (TDM) can guide the IV-to-SC switch.

Methods

Population pharmacokinetic (popPK) simulations were performed with previously published popPK models to explore the exposure profiles following various label and off-label IV-to-SC dosing scenarios (NONMEM 7.5).1-3 All virtual patients received IV IFX or VDZ at treatment weeks 0, 2, 6, 14, 22, and 30, and then switched to every two weeks (Q2W) or Q1W SC dosing.

Results

Following IV-to-SC switch according to label, the serum trough concentrations (Ctrough) will gradually increase over eight weeks (for IFX) and 16 weeks (for VDZ) before reaching the new steady state (SS) (Figure 1A-B). A linear relationship was observed between IV and SC Ctrough,ss for both drugs, allowing the prediction of SC Ctrough,ss hnbased on previous IV Ctrough,ss (Figure 1C-D).

Administering the first SC dose four instead of eight weeks after the last IV dose will hit SS much faster (immediately for IFX and in two months for VDZ), thereby allowing earlier TDM and avoiding the risk of temporary underexposure (Figure 2). Patients on Q6W or Q8W IV infliximab can safely switch to Q2W SC infliximab without a meaningful decrease in Ctrough,ss, while patients on Q4W IV infliximab need Q1W SC infliximab (Figure 3A). Vedolizumab Ctrough,ss will always be maintained after switching to Q2W dosing (Figure 3B).

While the Ctrough,ss target is easily maintained, it is more challenging to guarantee a stable eight-week averaged area under the concentration-time curve at SS (AUC8w,ss) upon switch. Surprisingly, switching to Q2W SC infliximab resulted in a lower AUC8w,ss than all possible IV infliximab dosing regimens used in clinical practice (Figure 3C). Only patients on Q4W IV vedolizumab should switch to Q1W SC dosing (Figure 3D). Depending on the belief whether it is Ctrough,ss or AUC that drives therapeutic response, patients who were on escalated IV dosing regimens may need Q1W SC to guarantee similar exposure before versus after switch (Table 1).

Conclusion

We performed popPK simulations to inform clinicians how to integrate TDM of IFX and VDZ into their clinical practice as a tool to monitor patients and guide decision-making on the optimal dosing strategy.

REFERENCES:

1. EMA/CHMP/548703/2019. European Medicines Agency. 2019.

2. Rosario et al. Aliment Pharmacol Ther. 2015.

3. Rosario et al. J Crohns Colitis. 13, S357 (2019).
P379 Effect of upadacitinib on inflammatory markers and clinical outcomes in patients with Crohn’s disease in the phase 3, U-EXCEL, U-EXCEED, and U-ENDURE studies
Authors: Vermeire S , Danese S , Cohen B L , Magro F , Chen Y , Ha C , Dubcenco E , Lacerda A P , Marced E , Oomen J , Garrison A , Peyrin-Biroulet L
Published: January 2023

Background

Improvement in clinical outcomes and normalisation of objective markers of inflammation, high-sensitivity C-reactive protein (hs-CRP) and faecal calprotectin (FCP), are considered treatment targets per STRIDE-II guidelines.1 We evaluated the effect of the oral selective Janus kinase inhibitor upadacitinib (UPA) on changes in hs-CRP, FCP, and clinical outcomes in patients with Crohn’s disease (CD).

Methods

In 2 phase 3, randomized, double-blind, placebo-controlled induction studies (U-EXCEL, NCT03345849; U-EXCEED, NCT03345836), patients with moderate-to-severe CD received 12-week treatment with UPA 45 mg (UPA45) once daily (QD) or placebo (PBO). Patients with clinical response to UPA45 were rerandomised in U-ENDURE (NCT03345823) to receive 52-week maintenance treatment with UPA 30 mg QD (UPA30), UPA 15 mg QD (UPA15), or PBO. Endpoints included marker normalisation (hs-CRP ≤ 5 mg/L, FCP ≤ 250 µg/g) in patients with elevated baseline marker levels, normal marker and clinical remission by Crohn’s Disease Activity Index (CDAI < 150) or very soft/liquid stool frequency (SF)/abdominal pain score (APS) (average daily SF ≤ 2.8 and average daily APS ≤ 1, neither greater than baseline), and ≥ 50% reduction from baseline in marker values with a decrease of at least 100 points in CDAI from baseline. Median changes from baseline in marker levels were also evaluated. Non-responder imputation with no special data handling for missing data due to COVID-19 was used.

Results

Of 1021 enrolled patients, 645 (63.2%) had elevated hs-CRP (> 5 mg/L) and 750 (73.5%) had elevated FCP (> 250 µg/g) levels at baseline. Significantly greater proportions of patients with elevated baseline marker levels achieved normalisation with UPA compared with PBO at week 12 (Fig 1A/B) and week 52 (Fig 2A/B; nominal P < .001 for all). Decreases in marker levels from baseline with UPA were observed as early as week 2 and were significantly greater than with PBO through week 12 (Fig 1C) and week 52 (Fig 2C; nominal P < .001 for all). Patients achieved clinical endpoints and improvements in markers at significantly higher rates with UPA45 vs PBO at week 12 (Fig 1D–F) and with UPA15 and UPA30 vs PBO at week 52 (Fig 2D–F; P < .001 for all). The safety profile of UPA in CD was previously reported and no new safety concerns were identified.

Conclusion

Improvements in clinical endpoints and normalisation of objective markers of inflammation were achieved as early as week 2 with UPA45 induction and sustained with UPA15 and UPA30 maintenance therapy in patients with CD. Median changes in hs-CRP and FCP with UPA support continued improvement of inflammation up to week 52.

1. Turner D., et al. Gastroenterology. 2021;160(5):1570–1583.
P380 Changes in faecal microbiome and metabolome are more pronounced in Crohn’s disease patients who adhered to the CD-TREAT diet and responded by calprotectin.
Authors: Svolos V , Hansen R , Russell R K , Gaya D R , Seenan J P , Macdonald J , Wilson D , Henderson P , Din S , Ho G T , Quince C , Ijaz U Z , Milling S , Nichols B , Papadopoulou R , McKirdy S , Gervais L , Shields S , Gerasimidis K
Published: January 2023

Background

Treatment with the CD-TREAT solid food diet improves disease activity indices, faecal calprotectin (FCAL) levels and quality of life in adults and children with active Crohn’s disease (CD); particularly in patients who adhere to the diet. Here we describe changes in faecal microbiome parameters during therapy with CD-TREAT and explore these changes against adherence.

Methods

Children and adult patients with active CD completed an 8-week treatment with CD-TREAT. The levels of FCAL, pH, total sulphide (colorimetry), short chain fatty acids (SCFA), branched chain fatty acids (BCFA) (gas chromatography), total bacterial load (qPCR for total 16S rRNA gene copy number/g) were measured in baseline faecal samples and at four and eight weeks of CD-TREAT. Liquid chromatography mass spectrometry (LC-MS) faecal metabolomics and 16s rRNA sequencing of the faecal microbiome were performed at the same timepoints. Since CD-TREAT is gluten-free, detection of the gluten immunogenic peptide (GIP) in faeces was used as an objective biomarker of treatment adherence. Data are presented as median (IQR).

Results

Forty patients [17 children, age: 14.0 (11.3-15.1) years; 23 adults, age: 33.9 (27.8-45.9) years] participated. Eighteen (45%) patients had detectable GIP in at least one of the two follow-up timepoints, suggesting incomplete adherence; the remaining 22 (55%) patients had undetectable GIP throughout the treatment course. Baseline FCAL levels decreased significantly in the group of patients with undetectable GIP [mg/kg, baseline: 1,190 (3,611-129); 8 weeks: 534 (92-1,230), p<0.05] but not in patients with detectable GIP [mg/kg, baseline: 599 (328-1,857); 8 weeks: 702 (278-1,496)]. During CD-TREAT, the concentration of faecal acetate, propionate, butyrate, total sulphide, total microbial load and faecal pH significantly changed in those with undetectable GIP but were less pronounced where GIP was detectable (Figure 1). Shannon diversity and richness significantly increased at both genus and OTU level, the abundance of several taxa changed, and LC-MS faecal metabolome shifted during CD-TREAT, but only in those with undetectable GIP (Figures 2 & 3).

Conclusion

We have identified that full adherence with CD-TREAT only occurs in ~55% of recipients, however a significant reduction in calprotectin is seen in those who adhere, and this is associated with microbial and metabolic changes which parallel those seen in successful exclusive enteral nutrition.