bluuebunny/crossref_metadata_2025 huggingface dataset:
P273 Defining the prognosis of children with Crohn Disease with the support of magnetic resonance enterography: a multi-center multi-reader study
Authors: Romanchuk A , Valle C , Ghirardi A , Bonaffini P A , Ippolito D , Sansotta N , Calia M , Zuin G , Sironi S , D’Antiga L , Norsa L
Published: January 2024

Background

Ileocolonoscopic assessment is the most accurate method for detecting intestinal inflammation in Crohn disease (CD), but it allows the assessment only of a limited tract of the small intestine and does not provide data on inflammation beyond the mucosa. The auxiliary use of magnetic resonance enterography (MRE) can overcome these limitations and allow to predict the course of CD. Paediatric Inflammatory Crohn's MRE Index (PICMI) is a multi-point index of intestinal inflammation (mucosal and transmural) in children with CD created on the basis of MRI. The aim of the present study is to assess whether this completely non-invasive index at diagnosis could predict the course of CD in children and to test the inter-reader agreement as surrogate of index reproducibility.

Methods

All children diagnosed with CD in two tertiary referral centres with a 1-year minimum follow-up were enrolled in the study. MRE at diagnosis was blindly evaluated by 3 expert radiologists and PICMI was calculated for all patients. Children’s disease was stratified according to PICMI at diagnosis into remission (<10), mild (11-55), moderate (56-120) and severe (>120). Inter-observer agreement among radiologist was calculated. Data at follow-up were collected at 6-8 weeks, 1 year, 3 years and 5 years after CD diagnosis. Association between PICMI at diagnosis and CD prognosis was evaluated.

Results

A total of 71 children (52 males) with proven CD were enrolled in the study and PICMI was calculated for 68. PICMI at diagnosis was stratified into remission 6 (8.8%), mild 29 (42.6%), moderate 24 (35.3%), severe 9 (13.2%). Inter-observer agreement was calculated with an intraclass correlation coefficient of 0.65 which indicates moderate reliability between the 3 raters. PICMI score at diagnosis significantly correlated with PCDAI (Paediatric Crohn's Disease Activity Index) at diagnosis (p: 0.036). Steroid-free remission at 1, 3 and 5 years was comparable between PICMI groups: remission + mild vs moderate + severe (p: 0.606). CRP and calprotectin negative steroid free remission at 1,3,5 was also comparable (p: 0.578). PICMI at diagnosis was associated with the probability of biologic introduction at 1 year: incidence rate ratio IRR: 2.17 (1.09-4.42); p=0.019, 3-year IRR: 2.12 (1.15-3.96); p=0.011, and 5 years: 2.21 (1.20-4.08); p=0.007 (figure 1).

Conclusion

PICMI score is a reliable and reproducible index to determine activity in children with Crohn’s disease. Children with more active disease at diagnosis according to PICMI have shown an increased need to progression to biologic treatment in order to gain a comparable rate of steroid free remission and inflammatory marker negativity if compared with children with lower PICMI scores.
P274 Renal failure in children with inflammatory bowel disease
Authors: Vuijk S , Klomberg R , Hellendoorn A , Kemos P , Aardoom M , Ruemmele F , Vrieling-Prince F , Croft N , de Ridder L
Published: January 2024

Background

Renal manifestations may occur in children with inflammatory bowel disease (IBD). The cause of renal manifestations is often unclear, but may occur as an extra-intestinal manifestation or due to IBD treatment. Renal complications can lead to acute renal failure, a severe complication and associated with a risk of developing chronic kidney disease (CKD). Current paediatric ECCO/ESPGHAN guidelines recommended to regular monitor renal function with calcineurin inhibitors. However, these recommendations are based on limited knowledge of renal manifestations in paediatric IBD. The aim of this study was to investigate the diagnosis and underlying causes of renal failure in children with IBD.

Methods

Cases of renal failure in children <19 years with IBD were collected from the international, prospective PIBDSETQuality Safety Registry1. A monthly survey was sent to participating paediatric gastroenterologists throughout the world asking to report cases of renal failure within their clinical practice. Renal failure was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 based on the Schwartz formula. Upon reporting a case of renal failure, a follow-up form was automatically sent to obtain more information about renal failure, IBD characteristics and outcomes (including CKD, defined as an eGFR <60 for >3 months).

Results

From November 2016 until August 2023, 220 gastroenterologists from 36 countries participated in the Safety Registry and 38 cases of renal failure were included. Characteristics at time of renal failure are reported in Table 1. Reported causes and diagnoses of renal failure are represented in Figure 1. Most frequently reported causes were IBD medication (n=12) and IBD itself (n=10). IBD medication included 5-ASA (n=5), tacrolimus (n=2) and one case of azathioprine or ibuprofen, vedolizumab, adalimumab, cyclosporine A and ciprofloxacin. Of the cases most likely caused by IBD itself, disease activity was remission (n=4), mild (n=2), moderate (n=3) or severe (n=1). In the majority of cases (n=26, 68%) creatinine was measured during routine follow-up, and not due to kidney-related symptoms. In 13/37 patients creatinine remained elevated after a median follow-up of 82 weeks [41-136 weeks]. Nine patients developed CKD, two patients required renal replacement therapy.

Conclusion

This is the first prospective study to report cases of renal failure in children with IBD. Renal failure can occur without symptoms, and may lead to CKD. Timely identification of cases of renal failure is important to adequately treat and monitor patients. We recommend to monitor creatinine in all children with IBD, independent of drug use, every 6 months.

References

1. Aardoom et al. BMJ Open. 2020
P317 Diagnostic accuracy of plasma calprotectin and serum calprotectin in patients with suspected Crohn’s disease
Authors: Rasmussen M H , Brodersen J B , Brasen C L , Madsen J S , Knudsen T , Kjeldsen J , Jensen M D
Published: January 2024

Background

Faecal calprotectin is a sensitive marker for chronic inflammatory bowel disease (IBD), and it correlates with the endoscopic disease activity. However, patient reluctance and handling in the laboratory are limitations for the clinical use, and there is a need for new reliable blood-based biomarkers. Prior studies indicate, that serum calprotectin (SCal) and plasma calprotectin (PCal) can be used as biomarkers for IBD, and SCal correlates better with disease activity in Crohn’s disease (CD) than in ulcerative colitis. The aim of this study was to investigate the diagnostic accuracy of SCal and PCal in patients examined for CD.

Methods

Patients with clinically suspected CD were enrolled in a prospective, blinded, multicentre study examining non-invasive modalities for diagnosing CD (ClinicalTrials.gov identifier NCT03134586). Patients had a standardized work-up including ileocolonoscopy, pan-enteric capsule endoscopy and blood samples within a 2-week period. EDTA plasma was prepared less than 2 hours of sampling by centrifugation at 3000 g for 15 minutes. Samples were stored in a biobank at − 80°C until further analysis. A routine C-reactive protein (CRP) was measured on the same day. SCal and PCal were analysed in batches using the calprotectin assay product nr.1201 from Gentian (Moss, Norway) on the Cobas platform (Roche, Basel, Switzerland). Analyses were performed in an ISO 15189 accredited laboratory.

Results

126 patients were enrolled in the study: 69 % women and 31 % men with a median age of 27.5 years (Table 1). A total of 57 (45%) patients were diagnosed with CD based on the result of ileocolonoscopy and pan-enteric capsule endoscopy. Patients with CD had a mean PCal of 0.50 mg/L (95% confidence interval (CI) 0.38-0.62) compared to 0.35 mg/L (CI 0.27-0.44) in non-CD patients (P = 0.03). The mean SCal was 1.45 mg/L (CI 1.20-1.69) and 1.06 mg/L (CI 0.90-1.22) in patients with and without CD, respectively (P = 0.01). Receiver operating characteristics curves showed an AUC of 0.63 (CI 0.53-0.73) for SCal and 0.61 (CI 0.51-0.71) for PCal, which was inferior to CRP (0.76, CI 0.68-0.85, P < 0.02) (Figure 1). In patients diagnosed with CD, SCal and PCal had a moderate correlation with CRP (rs = 0.47 and 0.55, respectively, P < 0.001), and SCal had a weak correlation with the Simple Endoscopic Score for CD (rs = 0.29, P = 0.04) and the Crohn’s Disease Activity Index (rs = 0.36, P = 0.03).

Conclusion

Levels of PCal and SCal are increased in patients with CD reflecting the systemic inflammatory response in this disease. However, SCal and PCal are insufficient biomarkers in patients with clinically suspected CD, and they are both inferior to CRP.
P320 Impact of Enterography on the Outcomes of Endoscopic Balloon Dilation for Ileocolonic Anastomotic Strictures in Crohn's Disease
Authors: Goncalves J , Lima Capela T , Cúrdia Gonçalves T , Magalhães J , Rosa B , Cotter J
Published: January 2024

Background

Ileocolonic anastomotic stricture (ICAS) is a common complication following surgery for complicated Crohn's Disease (CD). Endoscopic balloon dilation (EBD) has emerged as a non-invasive therapeutic modality for symptom relief and delaying surgical interventions. However, the impact of enterography, utilizing magnetic resonance imaging (MRI) or computed tomography (CT), in characterizing ICAS and its influence on short- and long-term EBD outcomes remain unclear.

Methods

This retrospective study included patients who underwent EBD for ICAS. Demographic and clinical data were collected, encompassing short-term outcomes (procedure complications and symptom improvement) and long-term outcomes (need for surgery, hospitalization, or repeat dilation).

Results

A total of 15 patients with ICAS were included in the study, with 46.7% being females, and a mean age of 41.2±15.6 years at the time of EBD. Six patients (40%) had undergone enterography six months prior to EBD. The median balloon diameter used for dilation was 15mm (range: 10mm to 17mm) and during the procedure, significant mucosal inflammation of the anastomosis (Rutgeerts Score ≥2) was observed in seven patients (46.7%). EBD was successful in 12 patients (80%) without any immediate complications. In the 12-month post-procedure period, one patient experienced hospital admission due to intestinal occlusion, one patient required abdominal surgery, and another patient underwent two additional EBD procedures. We did not observe a trend for an increased occurrence of complications in patients submitted to EBD without prior recent enterography, in the 12 months following the procedure or thereafter.

Conclusion

In this small but homogeneous cohort, our findings suggest that recent enterography does not significantly improve ICAS EBD outcomes. Therefore, our data suggest that performing enterography should not delay EBD in symptomatic CD patients with ICAS.
P329 Sarcopenia is a risk factor of post-operative recurrence of Crohn’s disease
Authors: Ceccarelli L , Rosi E M , Scandiffio R , Neri C M , Fe' P , Fornaroli G , Comparato C , Berti G , Baiano Svizzero G , Mumolo M G , D'Ischia R , de Bortoli N , Bellini M , Franceschi M , Costa F
Published: January 2024

Background

Sarcopenia is defined as reduction in skeletal muscle mass and muscle strength; it was found in up to 50% of patients with Crohn's disease (CD) in several studies.In CD patients sarcopenia is a risk factor for surgery, post-operative complications and worse surgical outcomes; furthermore, it is a negative prognostic factor for endoscopic remission in patients treated with biologics.The aim of our study was to evaluate the impact of sarcopenia on endoscopic recurrence at 6-12 months follow-up in CD patients after ileo-colic resection.

Methods

CD patients undergoing primary elective ileo-colic resection surgery between 2013 and 2023 were enrolled. Patients with previous intestinal surgery, pre-operative complications (abscess, perforation) and immunosuppressive or biologic therapy after surgery were excluded. Sarcopenia was defined as the sex- and height-adjusted Total Psoas Area Index (TPAI) lower than 5.4 cm2/m2 (men) and 3.56 cm2/m2 (women), calculated at the level of the third lumbar vertebra on MRI scans performed within 3 months before surgery. Already known risk factors for post-surgical disease recurrence were considered. Uni- and multi-variate analyses were performed to evaluate if sarcopenia before surgery could influence endoscopic recurrence (Rutgeers score ≥ i2) of disease 6-12 months after surgery.

Results

Seventy-two CD patients were included. Endoscopic recurrence (at 6-12 months follow-up colonscopy) was found in 22% of patients and it was associated with the presence of pre-operative sarcopenia (1.4% vs 15.3%;p<0.001) and surgical complications (2.78% vs 6.94%;p=0.024), while it was not associated with comorbidies, familiarity, smoke, extension of resection or pre-operative therapy, PCR and albumin. Sarcopenia was identify as predictor of endoscopic recurrence (OR=25;p=0.005) as well as surgical complications after resection (OR=99.7;p=0.032). Neither medical or surgical complications showed statistically significant correlation with the presence of pre-operative sarcopenia (p=0.819).

Conclusion

Sarcopenia in CD patients before surgery seems to be an independent prognostic factor for endoscopic recurrence. Perioperative interventions to improve sarcopenia may have positive impact on surgical outcomes and disease recurrence.
P352 Comparison of Radiation Dose, Image Quality, and Diagnostic Performance between Hybrid Iterative Reconstruction and Deep Learning Reconstruction for CT Enterography of IBD
Authors: He W , Xu P , Xu R L , Li X H
Published: January 2024

Background

CT enterography (CTE) is recommended as one of the preferred methods for patients with inflammatory bowel disease (IBD), especially in primary hospitals that lack MRI equipment. However, the potential risk of radiation derived from using CTE during the life-long follow-up is an important issue for these patients. This study aimed to compare the radiation dose, image quality, and diagnostic performance of CTE for IBD using hybrid iterative reconstruction (HIR) and deep learning reconstruction (DLR).

Methods

We prospectively collected data on low dose CTE reconstructed by HIR and DLR in patients with IBD between February 2023 and September 2023, and retrospectively enrolled IBD patients who underwent conventional dose CTE reconstructed by HIR between June 2019 and June 2022 as controls. The CTE examinations were performed within 2 weeks of bowel histologic evaluation (the reference standard of bowel inflammation). The objective and subjective image quality and the image features were evaluated by two IBD radiologists. The radiation dose, image quality, and diagnostic performance was compared between the two dose protocols.

Results

The preliminary study included 36 patients in the low dose group with HIR and DLR and 40 patients in the conventional dose group with HIR. There were no significant differences in demographic data of patients between the two groups (all P>0.05). The sensitivity, specificity, and diagnostic accuracy for detecting active inflammation were 71.4% (43.3%), 83.3% (80.0%), and 75.0% (52.5%) for the low dose group with DLR (HIR), respectively, and 84.4%, 62.5%, and 80% for the conventional dose HIR group. Low dose group with DLR resulted in significantly increased objective and subjective image quality and diagnostic confidence for active inflammation compared to low dose group with HIR (all P<0.05), with no inferiority to conventional dose group with HIR (all P>0.05). The dichotomous inter-reader reliability (k) for the entire group was 0.88. Low dose group resulted in a significant reduction in radiation exposure (mean [± SD], 2.20 ± 0.29 mSv) compared to conventional dose group (4.85 ± 1.96 mSv; P<0.001).

Conclusion

Low dose CTE with DLR significantly improved image quality compared to low dose CTE with HIR, and maintained similarly high diagnostic performance as conventional dose CTE with HIR. Importantly, the low dose CTE with DLR significantly reduced the radiation dose, improving the safety of CTE application in the life-long follow-up of patients with IBD.
P363 Multimodal dynamic ultrasound approach as predictor of response in patients with Crohn’s disease treated with ustekinumab
Authors: Mignini I , Maresca R , Esposto G , Ainora M E , Liguori A , Cintoni M , Galasso L , Laterza L , Lopetuso L R , Garcovich M , Riccardi L , Gasbarrini A , Scaldaferri F , Zocco M A
Published: January 2024

Background

Early prediction of the response to biological drugs in Inflammatory Bowel Diseases (IBD) is of utmost importance to allow prompt optimization of therapeutic strategies. Ustekinumab (UST) is nowadays a milestone in the treatment of Crohn’s disease (CD), but potential markers predicting its long-term efficacy are still lacking. Multimodal ultrasound (US), encompassing B-mode US, color-Doppler and contrast-enhanced US (CEUS), is a promising non-invasive technique, providing complementary information to endoscopy, due to its ability to both assess transmural healing and quantify changes in bowel microvascularization over time. The main objective of this study was to evaluate the role of multimodal US in predicting endoscopic response to UST in patients with CD. The secondary aim was to develop an US score that allows an early detection of treatment response.

Methods

We conducted a prospective monocentric study in the IBD outpatient clinic of Policlinico Agostino Gemelli in Rome, enrolling consecutive patients with moderate to severe ileal CD, who were scheduled to begin UST therapy as per clinical practice. Demographic, clinical and laboratory data were collected. Clinical activity was defined according to Harvey-Bradshaw Index. A complete US evaluation including B mode, Doppler, dynamic CEUS and elastography was perfomed at the time of induction (T0) and after 8 (T1), 16 (T2), 24 (T3) and 48 (T4) weeks of therapy. Each US parameter and their variations from baseline were correlated with endoscopic response (SES-CD reduction of at least 50% from baseline) and mucosal healing (SES-CD < 3) after 1 year.

Results

A total of 52 patients were included, 29 (55.8%) of which reached endoscopic response at T4. Median values of US parameters at the various time points were significantly different in the group who achieved endoscopic response from non reponders’ group (Figure 1). The univariate analysis showed that the percentage changes between T3 and T0 of bowel wall thickness, Limberg score (LS), mean signal intensity, rise time, wash-in rate (WiR), C reactive protein and Harvey-Bradshaw Index were associated with long-term therapeutic outcome (table 1). At the multivariate logistic regression analysis, three independent predictors of endoscopic response were selected: male sex, ∆%LS, and ∆%WiR. Based on the above parameters, we developed an US score that showed a good performance in predicting 1 year-endoscopic response (area under the curve: 0.91).

Conclusion

Multimodal ultrasound provides early predictors of the long-term therapeutic outcome in patients with CD treated with UST.
P365 Incidental terminal ileitis in asymptomatic patients. Is it Crohn’s disease?
Authors: Tsafaridou M , Theodoraki E , Foteinogiannopoulou K , Koutroubakis I
Published: January 2024

Background

Inflammation of the terminal ileum is a common finding during colonoscopy, even in patients without symptoms as an accidental finding. Nevertheless, there are no guidelines or wide consensus about the indications for treatment or follow-up, since the clinical importance and natural history of this entity has not yet been fully investigated.

Methods

This was a retrospective cohort study, where the electronic database of the Gastroenterology Department of University Hospital of Heraklion, Greece was searched through using the term "inflammation of terminal ileum" and "ulcers of terminal ileum", through the years 2012-2023. All cases with terminal ileitis as an accidental finding in asymptomatic patients, where colonoscopies performed for miscellaneous reasons (e.g. screening colonoscopy, follow-up colonoscopy after polypectomy) were identified. Patients with symptoms, or known Crohn’s Disease (CD) were excluded. Patients’ demographics, endoscopic and clinical follow-up data, as well as treatment and final diagnosis of CD were registered. Possible risk factors for terminal ileitis [smoking, use non-steroidal anti-inflammatory drugs (NSAIDs)] were also recorded. Univariate and multivariate analysis of the data was performed with SpSS v22 software.

Results

In a total of 465 cases with terminal ileitis 205 had known CD, 153 underwent colonoscopy for symptoms whereas 107 patients (62 females) underwent colonoscopy with no associated symptoms and constituted the study population. Among these 107 patients [median age 50, interquartile range (IQR) 39-64years, median BMI 25kg/m2, IQR 23.2-27.1kg/m2, median follow-up 4years) 27 (25%) patients were current smokers, 32 (30%) ex-smokers and 22 (20%) reported recent use of NSAIDS (Table 1).

During follow-up, 88 (82%) patients had a new colonoscopy with persistence of terminal ileitis in 66 (62%) of them, 68 (64%) developed symptoms, 37 (35%) were diagnosed with CD,39 (36%) received treatment, and 18 (17%) required hospitalization.

In the group of the patients that required treatment, only 8 (7.4% of the study population) eventually required systemic immunosuppression (corticosteroids, thiopurines, biologic agents.

In multivariate analysis, there was no statistically significant correlation between the persistent terminal ileitis on follow-up colonoscopy and BMI, the use of NSAIDs, or ex-smoking. Nevertheless, there was a significant correlation between active smoking and the persistence of terminal ileitis (p=.005).

Conclusion

Most of the patients with incidental, asymptomatic terminal ileitis remain asymptomatic and don’t require treatment. Close monitoring is required since diagnosis of Crohn’s disease is established in one third of them.
P373 Primary sclerosing cholangitis associated with inflammatory bowel disease: clinical characteristics of patients from reference centers in Brazil
Authors: da Silva B C , Chebli J M F , Ferreira S D C , Chebli L A , Evangelista R K A , Ribeiro T C D R , Alencar S R , Borges M D M , Lima G A S , Rzetelna H , Freire C C F , Parente J M L
Published: January 2024

Background

Inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC) are closely associated pathological entities that, when present in combination, create a phenotypically different disease, referred to as PSC-IBD. The occurrence of PSC complicating IBD seems to vary depending on the studied population. The aim of this study was to describe the clinical profile of patients with PSC-IBD in reference centers in Brazil.

Methods

Descriptive cross-sectional study in 7 tertiary centers. Patients with PSC and IBD were identified. Data were collected from patients' charts. The following variables were studied: age, age at diagnosis of IBD and PSC, type of IBD, Montreal classification, medications used, occurrence of colorectal cancer and dysplasia, colectomy and liver complications. The study was approved by the ethics and research committee.

Results

Ninety-three patients were included. The mean age of the patients was 43,8 years (range 17 to 73). 63 patients were male (67.7%). UC was more frequent 74.2% (N=69). The mean age at diagnosis of IBD and PSC was 31.4 years (range 6 to 67) and 35.6 years (range 8 to 72), respectively. The diagnosis of PSC preceded that of IBD in only 15 (16.1%) cases. Among patients with UC, the majority (61/69) had extensive colitis (88.4%), and 47.8% (33/69) had already used at least one biological therapy. Only 9 (13%) patients with UC required colectomy. Regarding CD, colon involvement occurred in 21 (87.5%) patients and 20 (83.3%) needed to use at least one biologic. Just 3 CD patients (12.5%) had isolated disease in the small intestine. In our study, liver cirrhosis occurred in 20 (21,5%) cases of the studied population, and 13 (14%) patients required liver transplantation. Fourteen (15,1%) IBD patients had dysplasia or colorectal cancer (CRC). Use of biological therapy was more frequent in patients with CD than in those with UC (83.3% vs 47.8%; p=0.002). There was a trend towards a higher occurrence of CRC in the UC population (p=0.08).

Conclusion

In our studied PSC-IBD population, UC was more common than CD. Furthermore, we observed that in this subgroup of IBD with PSC, UC presented a more severe phenotype, with a superior occurrence of extensive colitis and need for biological therapy. In CD, most patients have colonic involvement. Interestingly, we observed a greater need to use at least one biologic in CD patients (p=0.002), as well as the need to use multiple biologics compared to UC patients (p=0.009). Additionally, there was a trend towards greater occurrence of CRC in UC patients. The rates of occurrence of dysplasia and liver cirrhosis in our casuistic emphasize the demand for more intensive follow-up in patients with IBD and PSC.
P380 Integrated fecal metagenome and serum metabolome analysis revealed gut microbiome associated serum metabolites as diagnostic biomarkers for inflammatory bowel disease
Authors: Liu J , Huang L , Guo X , Dai X , Cao Q
Published: January 2024

Background

Gut microbiomes are altered among patients with IBD. Certain microbiome species were used as biomarkers for IBD diagnosis, yet with limited sensitivity and specificity, especially when used for the classification of UC and CD. Gut microbiome reprogramming was accompanied with metabolic shift. Previous studies discovered that gut microbiome-associated serum metabolites (GMSM) were disease-specific biomarkers with high sensitivity. The aim of this study is to explore how gut microbiome reprogramming is reflected in serum metabolome shift in IBD, and the potential of GMSM for IBD diagnosis and classification of UC and CD.

Methods

Shotgun metagenomic of stool and ultraperformance liquid chromatography-mass spectrometry based untargeted metabolomic profiling of serum samples from a discovery cohort of IBD and healthy individuals were performed. Spearman correlation analysis was used to identify GMSM that were differentially abundant among IBD and healthy individuals. Candidate GMSM for model construction were selected using LASSO and logistic regression. The selected GMSM panel was then transferred to multiple reaction monitoring based targeted detection. Diagnostic model for IBD and classification model for UC and CD were developed based on the GMSM panel using a training cohort, and then validated using an independent cohort consisting of patients with IBD, healthy individuals and patients with colorectal adenoma or non-adenoma polyps.

Results

Metagenome sequencing of fecal samples from 77 patients with IBD and 74 healthy individuals revealed significant shifts in gut microbiome, such as decrease in F. prausnitzii. Untargeted metabolomic profiling of serum from 76 patients with IBD and 28 healthy individuals revealed 724 differentially abundant metabolites, of which 151 metabolites were found to be significantly associated with gut microbiomes detected from the fecal samples (figure).

Candidate GMSM for model construction were established using the method described and the ultimate panel consisted of 17 metabolites, including 10 GMSM for diagnostic model for IBD and 7 GMSM for classification model for UC and CD. Eventually, the diagnostic model for IBD achieved an area under curve (AUC) of 0.98 in the training cohort, and 0.92 in the validation cohort. The classification model for UC and CD achieved AUC of 0.94 in the training cohort, and 0.9 in the validation cohort. In addition, the diagnostic model for IBD also effectively distinguished IBD from patients with colorectal adenoma or non-adenoma polyps (table).

Conclusion

Based on GMSM, we developed diagnostic and classification models for IBD with high specificity and sensitivity, providing an accurate and non-invasive approach for IBD diagnosis and classification of UC and CD.
P430 The influence of persistent organ damage on IFX pharmacokinetic modeling and disease progression assessment: findings from a prospective real-world study in inflammatory bowel disease patients
Authors: Magro F , Fernandes S , Patita M , Arroja B , Lago P , Rosa I , Tavares de Sousa H , Ministro P , Mocanu I , Vieira A , Castela J , Moleiro J , Roseira J , Cancela E , Sousa P , Portela F , Correia L , Moreira P , Afonso J , Dias S , Danese S , Peyrin-Biroulet L , Vucicevic K , Santiago M
Published: January 2024

Background

Effective management of inflammatory bowel disease (IBD) relies on a comprehensive understanding of infliximab (IFX) pharmacokinetics (PK). This study's primary goal was to develop a robust PK model, identifying key covariates influencing IFX clearance (CL), while concurrently evaluating the risk of disease progression during the maintenance phase of IBD treatment.

Methods

The multicenter, prospective, real-world DIRECT study was conducted in several care centers, which included 369 IBD patients in the maintenance phase of IFX therapy. A two-compartment population PK model was used to determine IFX CL and covariates. Logistic and Cox regressions were applied to elucidate the associations between disease progression and covariates embedded in the PK model.

Results

The PK model included the contributions of weight, albumin, antidrug antibody (ADA), and fecal calprotectin (FC). On average, higher ADA, FC concentration and weight, and lower albumin concentration resulted in higher IFX CL. In the multivariate regression analyses, FC levels influenced the odds of disease progression in all its different definitions, when adjusted for several confounding factors (Fig. 1). Additionally, alongside FC, both IFX and C-reactive protein demonstrated a significant impact on the temporal aspect of disease progression.

Conclusion

In this 2-year prospective real-world study, readily available clinical covariates, notably FC, significantly impacted IFX availability in IBD patients. We demonstrated that persistent gut damage, as mirrored by FC, substantially influenced IFX clearance. Importantly, FC emerged as a pivotal determinant, not only of IFX pharmacokinetics but also of the progression of the underlying disease. These findings underscore the imperative need to integrate FC into forthcoming IFX pharmacokinetic models, amplifying its clinical significance.
P462 The burden of mental health disease in people with inflammatory bowel disease - Crohn's Colitis Cure (CCC) Data Insights Program
Authors: Mcnamara J , Wilson W , Pipicella J L , Ghaly S , Gearry R , Williams A , Lynch K , Lawrance I , Schultz M , Walker G , Radford-Smith G , Connor S J , Andrews J M
Published: January 2024

Background

The impact of Inflammatory Bowel Disease (IBD) on individuals’ quality of life is well reported. Recent studies have shown that depression or anxiety affect almost 1 in 5 people with IBD and may be a predictor of active disease. We aimed to explore the burden of MHI in the Australasian IBD population and examine the real-world variation in screening and care across different sites and care settings

Methods

Crohn’s Colitis Care’s (CCCare) clinical quality registry (CQR) is created by deidentified data flowing across from routine care encounters. Data in the CQR for all individuals with a clinical encounter since August 2018 were interrogated in April 2023. Mental health data were collected from documentation during routine care or through patient consumer completion of embedded questionnaires, namely Depression Anxiety and Stress Scale 21 [DASS-21] and Kessler Psychological Distress Scale [K10]

Results

The CQR contained 6614 people with IBD with a mean age of 44.4 (SD +/- 22.09) and even gender distribution (50.9% female). 79.5% of people were from Australia and 20.5% from New Zealand. 57.1% of people had Crohn’s disease (CD), 40.4% ulcerative colitis (UC) and 2.5% IBDU with a mean disease duration of 13.3 years (SD +/-23.0). Anxiety was the 4th most listed comorbidity affecting 17.8% of individuals, depression 7th affecting 13.7% of people and both depression and anxiety 13th affecting 9.1% of people with IBD. In total 40.8% or 2 in 5 people with IBD in Australasia had received a formal diagnosis of a MHI.

2,928 consumers had been invited to complete the DASS-21 and 2,340 the K10 (44% & 35% respectively). Of the questionnaires sent, 32% of DASS-21s and 33% of K10s were completed. Rates of both invitation and completion varied significantly between centres. Invitation rates varied from 11% - 90% (p<0.001) while questionnaire completion rates varied from 26% to 46.8% (p<0.001).

The mean DASS-21 score for all people with IBD was 8.1 for depression (7-10 indicating moderate disease), 6.6 for anxiety (6-7 suggests moderate disease) and 11.2 for stress (10-12 indicates moderate disease). Individuals with current fistulising CD (representing severe IBD phenotype) mean DASS-21 scores were higher than the wider IBD population, averaging 9.9 for depression (p<0.001), 7.4 for anxiety (p<0.001) & 12.9 for stress (p<0.001)

Conclusion

Individuals with IBD suffer from high rates of MHIs, with those suffering more severe disease phenotypes scoring worse on mental health assessment tools. Despite the availability of screening and monitoring tools, healthcare providers use these variably and insufficiently. This may result in unmet care needs. Standardisation of care addressing the psychosocial care needs of people with IBD is needed
P464 Could Chat Generative Pre-Trained Transformer (ChatGPT) be an AI-provided friend of the patients for frequently asked questions concerning their IBD management? An evidence- and guidelines-controlled textual analysis of AI-provided outputs
Authors: Gravina A G , Pellegrino R , Palladino G , Imperio G , Ventura A , Auletta S , Cipullo M , Ciamarra P , Dallio M , Federico A
Published: January 2024

Background

Artificial intelligence (AI) is gradually and potentially entering the everyday lives of patients with Inflammatory Bowel Disease (IBD). Systems such as Chat Generative Pre-Trained Transformer (ChatGPT), based on large language models (LLM), are now within reach. It is necessary to weigh whether these LLM systems can be real generators of medical information and whether the latter is generated based on credible databases and evidence. This study evaluated and analysed whether the outputs of ChatGPT to common questions from IBD patients can provide credible and scientifically reliable outputs.

Methods

IBD-expert physicians retrieved a list of ten IBD frequently asked questions in their clinical practice. The ten with the highest frequency (Q1-10) were collected from the total number of questions and then input on ChatGPT (see Table) on three different days (18th, 19th, and 20th August 2023), and each output generated by the chatbot was categorised as O1, O2, and O3. The same research team evaluated the AI-generated responses by ChatGPT for each question by objectively comparing them with the available evidence (provided by meta-analyses, systematic reviews and ECCO guidelines).

Results

Q1 O1-3 were reliable, with a correct definition of the absence of definitive therapy for IBD. In Q2 O1-3, ChatGPT failed to clarify the lack of solid evidence for nutritional therapy in IBD. Q3 O1-3 provided corrected guidance on repeat endoscopic examinations for IBD. Q4 O1-3 did not provide reliable answers on removing topical therapy in ulcerative colitis. In Q5 O1-3 good advice was given to the IBD patient on how to plan a pregnancy. Q6 O1-3 brought out the lack of ChatGPT update (stopped in September 2021), limiting the range of new oral small molecule therapies available for the IBD patient. In Q7 O1-3 ChatGPT correctly outlined the need for individual risk stratification for endoscopic surveillance of colorectal cancer. In Q8 and Q9 O1-3 ChatGPT correctly weighed the risk of infection/cancer during biologic therapy and how heritability is only one piece of the pathogenetic puzzle of IBD. Finally, in Q10 he correctly elucidated the possibility of biological therapy preventing post-operative recurrence of Crohn's disease.

Conclusion

ChatGPT is a potentially useful complementary tool for communicating with IBD patients. It is necessary to improve the degree to which it is updated and sources on appropriate databases (e.g., Scopus, Web of Science, and MEDLINE). Ultimately, there are still significant limitations. Much of the latest findings, in fact, are excluded from ChatGPT evaluation. A portion of the outputs provided are partially incorrect or not fully detailed and not yet ready to be released to the patient without a physician filter.
P494 Efficacy and safety of Upadacitinib in moderate to severe paediatric Crohn’s disease and ulcerative colitis in a tertiary Paediatric IBD (PIBD) centre – A case series
Authors: Kontaki E , Merchant A , Gaynor E , Kiparissi F
Published: January 2024

Background

Upadacitinib is a selective Janus kinase 1 inhibitor approved for the treatment of patients 18 years and older with the diagnosis of Crohn’s disease and ulcerative colitis. Although there is promising data for its use in adult inflammatory bowel disease (IBD), limited data are currently available on its use in paediatric IBD. We present our experience in this case series of patients ≤ 18 years on Upadacitinib.

Methods

We identified patients under the age of ≤ 18 years, started on Upadacitinib for the indication of IBD. Data on demographics, disease subtype, duration on Upadacitinib, number of biologic failures, tofacitinib use, concomitant biologic use, adverse events and clinical remission were gathered.

Results

12 patients with paediatric IBD (median age at Upadacitinib start 15.5 years, range 13.9 to 17.8 years, 8 (67%) males, were identified. 7 patients had Crohn’s disease, 3 patients had ulcerative colitis and 2 patients had IBD unclassified. 4 patients (33%) were diagnosed under the age of 6 years with early onset IBD (EOIBD), 1 was 3.5 years old, 1 was 4 years old and 2 were 5 years old. 11/12 (92%) patients had failed 3 or more biologics. Upadacitinib was used as monotherapy in all patients and previous biologic treatments were stopped. 1 patient with a partial response to tofacitinib was switched to Upadacitinib. All patients had active disease at commencement of Upadacitinib. All 12 (100%) patients were started on 45 mg of Upadacitinib. 8/12 (67%) patients have been followed up for at least 8 weeks. Out of the 8 patients, 5/8 (63%) patients were in clinical remission between 8-16 weeks of therapy, 2/8 (25%) had partial response and 1/8 (13%) has been refractory to treatment. Relapse of symptoms was noted in 1 patient after dose was dropped to 30 mg; this patient had achieved remission on 45 mg. No serious adverse events occurred; 2 patients noted to have increased triglycerides (max 5.75mmol/L; range 0.38-1.58mmol/L). 1 of them had previous exposure to tofacitinib and the triglycerides were already raised prior to starting Upadacitinib. 1 patient developed headaches, as a result, Upadacitinib dose was decreased. There were no incidences of shingles or other serious infections.

Abbreviations

CD, Crohn's disease; UC, ulcerative colitis; IBD-U; inflammatory bowel disease unclassified; Upa, upadacitinib; AEs; adverse events

Conclusion

The patients in this case series, started on Upadacitinib, are a heterogeneous group with refractory disease. In these paediatric and adolescent patients Upadacitinib seemed safe and efficacious with a low side effect profile. Further national and international collaborative studies are needed to confirm our findings.

Table 1. Patient Characteristics
P515 Exclusive enteral nutrition downstages complicated Crohn’s disease prior to surgical resection: A feasibility study
Authors: Zuk D , Jaksic D , Andersson S , Soop M
Published: January 2024

Background

Exclusive enteral nutrition (EEN, oral or enteral liquid feeds only) is an established first-line therapy to induce remission in Crohn’s disease (CD) in children, but not in adults where low tolerance has been reported. Recently, smaller studies have suggested advantages of EEN in preoperative optimisation in adults. We hypothesise that in this setting, EEN is feasible and is associated with improved inflammatory and nutritional markers.

Methods

Consecutive patients with small bowel or ileocolic Crohns disease, who started preoperative EEN at two large IBD centres 2020-2023 were retrospectively studied. EEN was part of a 4-6week preoperative optimisation pathway. Outcomes were compliance and serum albumin, c-reactive protein and body weight, respectively. Medians (range) & Wilcoxon tests used.

Results

Thirty-two patients started EEN for stricturing (n=10) or penetrating disease (n=14). Six patients (19%) did not tolerate EEN and received parenteral nutrition (n=2) or reverted to normal diet (n=4), while 26 patients (81%) completed EEN until surgery. This group received EEN during 38 (17-70) days. C-reactive protein concentrations decreased from 8.5 (1-157) to 3 (1-96) mg/L (p = 0.0051), and albumin levels increased from 33.5 (27-44) to 38 (26-42) g/L (p< 0.001), while body weight did not change, from 67 (48.5-107) to 66.6 (48.5-105.7) kg (p = 0.25). 21 (81%) EEN patients underwent minimally invasive surgery, 22 (85%) had a primary anastomosis and 4 a stoma. Median postoperative length of stay was 4 (2-11) days. One patient with a severe complication, no one with an anastomotic leakage.

Conclusion

EEN was well tolerated in this cohort of patients undergoing surgery for complicated CD. EEN was associated with improved systemic inflammation, a maintained nutritional status, and favourable postoperative outcomes despite the complexity of disease in this group of patients. These results align with previous studies that have shown the effectiveness of EEN in reducing disease activity and promoting mucosal healing in CD patients.By reducing inflammation and uphold nutritional status, EEN might help to create a more favourable surgical environment, potentially leading to better outcomes and decreased postoperative complications.
P548 Ustekinumab shows favourable safety profile and drug persistence rates in patients with Crohn’s Disease – results from a tertiary IBD centre
Authors: Snehali M , Ahmed A , Ghosh S , Iacucci M , Shivaji U N
Published: January 2024

Background

Patients with Crohn’s disease (CD) often require multiple biological therapies due to loss of response. Anti-TNF drugs are generally used as first-line biologic followed by a switch of class when patients lose response. Ustekinumab (UST), an IL12/23p40 antagonist is used in CD, often after anti-TNF failure. The aim of the study was to report on outcomes of UST therapy with a median follow-up period of nearly 24 months.

Methods

All CD patients who commenced UST therapy were identified from EMR at two tertiary referral centers between January 2017 and December 2021. All relevant demographic and clinical data were collected. Data on clinical response (defined as a downgrade in disease activity based on clinician assessment & biochemical parameters), steroid-free duration, and long-term response to UST at 52 and 104 weeks were recorded. The response was assessed clinically and supported by biomarkers, cross-sectional imaging, endoscopic data, and sustained maintenance of UST. Statistical analysis was carried out using the IBM® SPSS® Statistics software package Version: 28.0.0.0.

Results

A total of 249 CD patients (M=133 (53%); median age 41 years) were included, with a median follow-up period of nearly 24 months (5-79 months). 94 (38%) patients had stricturing (B2), penetrating (B3) and perianal phenotype at baseline and 104 (42%) had undergone previous resection/s. 207 (83%) had documented moderate to severe disease activity and 211 (85%) patients were exposed to at least one biologic prior to treatment with UST. 66 (27%) patients were on concomitant thiopurines at the start of treatment. 224 (90%) patients in our cohort showed clinical response to UST and all remained on treatment at the end of follow-up period. The distribution of patients as per disease activity at baseline, 52 and 104 weeks is illustrated in Figure 1. An improvement in haemoglobin levels was observed post-therapy with UST, which was statistically significant at 104 weeks (p<0.001), with corresponding significant reduction in faecal calprotectin levels (median reduction: 506 mcg/g to 335 mcg at 104w; p<0.001). Only 10 (4%) patients had side-effects which were directly attributed to UST therapy.

Conclusion

UST is an effective therapeutic option in CD for both bio-naïve and previous biologic failure patients. Although our cohort had a large proportion of patients with complicated and refractory disease, clinical response was observed, regardless of their previous exposure status to biologics, and disease phenotype. UST appears to be well tolerated with a reasonable safety profile. UST has good drug-persistence rates making it economically feasible in the long term. Clinicians could safely continue UST for longer durations to manage CD.
P568 Clinical relevance of baseline and change in Urgency Numeric Rating Scale score for mirikizumab treatment for Ulcerative Colitis
Authors: Clemow D , Dubinsky M C , Baygani S , Sands B E , Keohane A , Danese S , Travis S , Schreiber S , Walsh A , Hibi T , Hunter Gibble T , Moses R
Published: January 2024

Background

Mirikizumab (MIRI), an anti-IL-23p19 antibody, has demonstrated efficacy/safety in moderately-to-severely active ulcerative colitis (UC) Phase 3 trials (LUCENT-1 and -2; NCT03518086, NCT03524092). This analysis evaluated induction and maintenance efficacy of MIRI among patients with different baseline (BL) bowel urgency severity.

Methods

In LUCENT-1, patients were randomized to receive 3 intravenous doses of 300mg MIRI or placebo (PBO); 1 every 4 weeks (Q4W). In LUCENT-2, responders to MIRI induction at W12 were rerandomized to subcutaneous 200mg MIRI or PBO Q4W through W40 (52W continuous treatment). Endpoints: clinical response, clinical remission, endoscopic remission, symptomatic remission at W12 and W52 (definitions in figure legend), Urgency Numeric Rating Scale ([UNRS]: 11-point scale from 0 [no urgency] to 10 [worst possible urgency]). Analysis: Fisher's exact test with non-responder imputation by patient induction BL UNRS score: 0-3, 4-6, and 7-10; score cut-offs based on ≥3 being a clinically meaningful improvement (JPRO 2022;6:114).

Results

Number of patients by BL UNRS score of 0-3, 4-6, or 7-10: W12 – 149, 437, 576 patients, respectively; W52 – 70, 215, 259 MIRI responders. At W12 and W52, a significantly greater proportion of MIRI-treated patients achieved clinical response, clinical remission, endoscopic remission, and symptomatic remission, regardless of UNRS score group at induction BL, for all comparisons except W52 clinical remission score 0-3 (Figure 1). In general, across clinical endpoints and regardless of BL UNRS score, MIRI treatment improved UNRS scores at W12 and W52 for a majority of patients, regardless of achievement of the clinical endpoint, although to a lesser extent when not achieved. MIRI treatment improved UNRS scores at W12 and W52 to a greater extent than PBO treatment regardless of achievement of clinical endpoint (Table 1; clinical remission data shown). Regardless of BL UNRS score, individual-point score shift data (not shown) illustrated that score shifts generally were distributed across lower scores at W12 and W52 than BL. This is relevant since Dubinsky and colleagues (JPRO 2022;6:31) demonstrated that a UNRS 1-2-point change in score can be important to a patient.

Conclusion

Regardless of BL bowel urgency severity based on UNRS score, MIRI is efficacious in achieving symptomatic, endoscopic, and clinical endpoints in UC patients. MIRI improves bowel urgency severity vs PBO even if clinical endpoints are not achieved. Observing shifts in UNRS scores along the UNRS scale, regardless of starting point, may aid in understanding a patient’s efficacy outcomes. These results support MIRI’s efficacy in bowel urgency and the clinical relevance of bowel urgency severity assessment over time.