Introduction

A small but significant proportion of patients with Crohn’s disease (CD) will ultimately require a permanent ileostomy. (1-3) The natural history and treatment success in these patients remain unclear and studies on endoscopic recurrence are lacking. The aim of this study was to investigate the endoscopic recurrence rate, possible risk factors, and treatment outcomes with current biological agents.

Aims & Methods

We performed a retrospective study of CD patients with a permanent ileostomy in a tertiary referral center. Inclusion criteria were CD adults (≥16 years) and the presence of an ileostomy for at least 12 months. Ileal postoperative recurrence was defined as the presence of ulcerations during ileoscopy. Traditional risk factors historically associated with postoperative recurrence (age at diagnosis ≤16 years, active smoking, penetrating phenotype, and inflammation at resection margin) were evaluated. (4,5) The probability of developing post-operative ileitis was examined by cox regression and Kaplan Meier analysis.

Results

166 patients were identified (median age 34 years (IQR 24-46), 63% female) (Table 1). Median follow-up after surgery was 5.5 years (IQR 2-14) and 37% had a loop ileostomy without resection. 115/166 (69%) underwent endoscopy during follow-up. Indications for ileoscopy were symptoms of flare (50%), planning for ostomy closure (14%) and other indications (21%). Endoscopic lesions were observed in 40% of patients, with a cumulative risk at 1-, 3- and 5-years of 13%, 27% and 36%, respectively. Controlling for traditional risk factors, patients with preoperative anti-TNF treatment were at higher risk (HR 2.18, 95% CI 1.11-4.28), with 17%, 41%, and 44% recurrence rates at 1, 3, and 5 years respectively (log rank P = 0.01). Other traditional risk factors for postoperative recurrence were not predictive of endoscopic disease recurrence in this cohort. Ileal recurrence was treated with biological therapy, including infliximab, adalimumab, vedolizumab, or ustekinumab. Patients treated with vedolizumab had the highest rate of remission (6/8 patients) and longest treatment persistence (54 months, IQR 19-102.8) (Table 1).

Table 1	All patients (N=166)	Endoscopic surveillance (N=115)
Female, n (%) Median age at diagnosis, years (IQR)	105 (63.3) 22.0 (16.8-31.0)	77 (67.0) 22.0 (16.0-30.0)
Median disease duration at time of surgery, years (IQR)	7.0 (2.0-15.0)	7.0 (2.0-13.0)
Smoking status at time of surgery, n (%) Never Former Current Unknown	89 (53.6) 29 (17.5) 36 (21.7) 12 (7.2)	68 (59.1) 26 (22.6) 16 (13.9) 5 (4.3)
Disease location and behaviour at diagnosis, n (%) L1, ileal L2, colonic L3, ileocolonic Unknown location B1, inflammatory B2, stricturing B3, penetrating Unknown behaviour Perianal disease at time of surgery, n (%)	13 (7.8) 95 (57.2) 42 (25.3) 16 (9.6) 71 (42.8) 13 (7.8) 28 (16.9) 54 (32.5) 74 (44.6)	11 (9.6) 67 (58.3) 30 (26.1) 7 (6.1) 54 (47) 7 (6.1) 20 (17.4) 34 (29.6) 51 (44.3)
Previous intestinal resection, n (%)	86 (51.8)	55 (47.8)
Previous immunomodulator, n (%) Previous biological therapy, n (%) Previous anti-TNF ≥2 prior biologicals	109 (65.7) 125 (75.3) 102 (61.4) 32 (19.3)	79 (68.7) 88 (76.5) 71 (61.7) 23 (20)
≥1 traditional risk factor*, n (%)	138 (83.1)	95 (82.6)
Endoscopic recurrence, n (%)		46 (40)
Endoscopic remission after treatment, n (%) Infliximab Adalimumab Vedolizumab Ustekinumab		4/13 (20.8) 7/13 (53.8) 6/8 (75) 4/12 (33.3)

* Defined as age at diagnosis ≤16 years, active smoking, penetrating phenotype, history of IBD-surgery and inflammation at resection margin.

Conclusion

This retrospective study showed that 40% of ileostomy patients developed endoscopic recurrence. Patients with previous anti-TNF exposure were at higher risk of recurrence. Vedolizumab was the most effective treatment, although this finding needs to be confirmed in larger cohorts.

References

1. Cosnes, J., Gower-Rousseau, C., Seksik, P., & Cortot, A. (2011). Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology, 140(6), 1785–1794. https://doi.org/10.1053/j.gastro.2011.01.055
2. Ma, C., Almutairdi, A., Tanyingoh, D., Seow, C. H., Novak, K. L., Lu, C., Panaccione, R., Kaplan, G. G., & Kotze, P. G. (2019). Reduction in surgical stoma rates in Crohn's disease: a population-based time trend analysis. Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland, 21(11), 1279–1287. https://doi.org/10.1111/codi.1473
3. Everhov, Å. H., Kalman, T. D., Söderling, J., Nordenvall, C., Halfvarson, J., Ekbom, A., Ludvigsson, J. F., Olén, O., & Myrelid, P. (2022). Probability of Stoma in Incident Patients With Crohn's Disease in Sweden 2003-2019: A Population-based Study. Inflammatory bowel diseases, 28(8), 1160–1168. https://doi.org/10.1093/ibd/izab245
4. Gionchetti P, Dignass A, Danese S, Magro Dias FJ, Rogler G, Lakatos PL, et al. 3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn's Disease 2016: Part 2: Surgical Management and Special Situations. J Crohns Colitis. 2017;11(2):135-49.
5. Lamb CA, Kennedy NA, Raine T, Hendy PA, Smith PJ, Limdi JK, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019;68(Suppl 3):s1-s106.

Disclosure

Geert D’Haens has served as advisor and/or speaker for Abbvie, Alimentiv, Astrazeneca, Bristol Meiers Squibb, Boehringer Ingelheim, Celltrion, Ferring, Eli Lilly, Galapagos, Glaxo Smith Kline, Immunic, Index Pharmaceuticals, Johnson and Johnson, Polpharm, Prometheus biosciences, Prometheus laboratories, Procise diagnostics, Protagonist, Sandoz, Takeda, Tillotts, Ventyx.

Introduction

The BELCOMID study recruited immune mediated inflammatory disease (IMID) patients during the COVID19 pandemic. Patients were evaluated before vaccination, after onset of the vaccination campaign and after onset of booster vaccinations. Clinical data, Nucleocapsid(N-)antibodies and Spike(S-)antibodies were assessed.

Aims & Methods

Current subgroup analysis aimed to firstly, explore factors associated with N-/S-antibody response in IMID patients with different COVID19 vaccination status. Five patient groups were identified. G1: no vaccination before the vaccination campaign, G2: complete baseline vaccination, G3: 1 booster, G4: 2 boosters, G5: patients refusing every vaccine even after the booster campaign. We report on influence of IMID treatment and smoking status.
Secondly, we explored influence of SARS-CoV2 infection and vaccination on IMID flare-up.

Results

Demographics of 2165 recruited IMID patients are shown in Table.
After baseline vaccination (G2) odds of N-seroconversion were higher in patients treated with combined IMM/TIMT (OR2.52, p=0.023). No other association with N-seroconversion was found.
Mean S-antibody titre increased progressively from G2 to G4. After completed baseline vaccination (G2), odds of S-antibody seroconversion were lower in those treated with TIMT (OR0.28, p=0.0079) particularly rituximab (OR0.0354, p<0.001), IMM (OR0.276, p<0.001), combined IMM/TIMT (OR0.156, p<0.001) and systemic steroids (OR0.183, p<0.001). IMID flare prior to vaccination was associated with lower risk of S-seroconversion (RR0.94, p<0.001). By contrast, mean S-titre was higher for those treated with antiIL23 (mean ratio 2.17, p=0.011) and vedolizumab (mean ratio 1.84, p<0.001) in G2.
After 1 booster (G3), lower odds of S-seroconversion remained with rituximab (OR0.0368, p<0.001), IMM (OR0.222, p=0.0014), combined IMM/TIMT (OR0.15, p<0.001) or systemic steroids (OR0.0637, p<0.001). Vedolizumab was associated with lower odds of being in the lowest S-titer quartile (OR0.206, p<0.001). Odds for S-antibody seroconversion with anti-TNF were higher compared to rituximab both for patients in G2 (OR26.3, p<0.001) and G3 (OR27.5, p<0.001).
Patients who received 2 boosters (G4) all had S-seroconversion and no IMID treatment modality was associated with higher odds of being in the lowest quartile.
After baseline vaccination (G2) smokers had higher risk of being in the lowest S-antibody titer quartile (RR1.45, p=0.0098). This observation persisted after 1 booster (G3)(RR1.42, p=0.0122) but was no longer noticed after 2 boosters (G4).
After start of booster vaccinations, 25.17% of patients had experienced IMID flare-up in the previous months. No significant association between IMID flare-up rate and previous SARS-CoV2 infection was found. There was no increased risk of IMID flare-up with additional booster vaccination. However, patients who received 2 booster vaccines showed a lower RR for IMID flare-up compared to those who only received 1 booster (RR0.70, p=0.0067).

	G1 (N: 2144)	G2 (N: 1532)	G3 (N: 1283)	Group 4 (N: 147)	Group 5 (N: 40)
Mean age (SD)	44.6 (35.5)	46.9 (30.8)	46.6 (32.7)	51.0 (15.7)	39.4 (14.4)
Male/female	1088 (51.0%)/1047 (49.0%)	794 (51.9%)/737 (48.1%)	661 (51.6%)/621 (48.4%)	80 (54.4%)/67 (45.6%)	24 (60.0%)/16 (40%)
Active smoker	369 (17.2%)	261 (17.0%)	201 (15.7%)	24 (16.3%)	12 (30.0%)
TIMT (targeted treatment)	1580 (73.7%)	1232 (80.4%)	1073 (83.6%)	119 (81.0%)	38 (95.0%)
IMM (immunomodulator)	456 (21.3%)	311 (20.3%)	225 (17.5%)	39 (26.5%)	8 (20.0%)
IMM+TIMT combined	263 (12.3%)	197 (12.9%)	152 (11.8%)	24 (16.3%)	8 (20.0%)
Recent systemic steroids	229 (10.7%)	91 (5.94%)	59 (4.60%)	6 (4.08%)	4 (10.0%)

Conclusion

Certain immune-modulating treatment modalities and smoking may blunt serologic COVID19 vaccination responses. However, this is overcome by repeated booster vaccination without increased risk of IMID flare-up.

Disclosure

The BELCOMID study group received research grants from following pharmaceutical companies: Almirall, Roche, Janssen, Pfizer, Eli Lilly, Amgen, Biogen, Mylan, LEO Pharma. These companies had no role in study design, conduct nor reporting of results.

Introduction

Perianal fistulising Crohn’s disease (PFCD) affects up to 20% of patients with Crohn’s Disease (CD). PFCD can cause pain, purulent discharge and faecal incontinence, leading to significant morbidity and reduction in quality of life. The use of biologic therapy, antibiotics and surgical intervention remain the mainstay of management of perianal fistulas.

Aims & Methods

This study aims to review current practices in the management of PFCD across two large tertiary IBD centres. This retrospective cohort study assessed adult patients with PFCD between two tertiary Australian hospitals between 2006 to 2024. Patients with PFCD were identified using prescribing data. CD phenotype, therapy and fistula-related data were extracted. Biologic choice and therapeutic drug monitoring, antibiotic choice and duration, surgical intervention, and length of stay in hospital were monitored. Cross-sectional disease activity of perianal fistulizing disease was assessed at the time of data collection using clinical fistula symptom grade and radiological assessment were available. Clinical remission was defined as fistula symptom grade of 1 or less. Radiological remission was defined by healing fistula tracts or no active inflammation seen on MRI. The study was approved by the Central Adelaide Local Health Network Human Research Ethics Committee (HREC19145).

Results

Gender Male, n Female, n Age, y, median (IQR)	n = 57 30 27 40 (31-54)
Active Smoker, n (%)	14 (24.5)
Median length of clinical follow up, months, n (IQR)	46.5 (23.8-72.3)
Antibiotics Prescribed Metronidazole, n treated (%) Amoxicillin / Clavulanic acid, n treated (%) Others, n treated (%)	47 (68.1) 13 (27.7) 9 (4.2)
Duration of Antibiotics Metronidazole, median duration, days (IQR) Amoxicillin / Clavulanic acid, median duration, days (IQR) Others, median duration, days (IQR)	5 (5-7) 5 (5-10) 14 (7-14)
Biologic therapy Total patients on biologic therapy, n (%) Infliximab, n (%) Adalulimab, n (%) Ustekinumab, n (%)	56 (98.2) 43 (75.4) 11 (19.3) 2 (3.5)
Therapeutic Drug Monitoring (Infliximab) Infliximab level performed, n (%) Subtherapeutic (Infliximab level <10), n (%) Active disease and subtherapeutic (Infliximab level <10), n (%)	37 (86%) 30 (81.1%) 12 (40%)
Remission status Clinical Remission, n (%) - Defined as Fistula symptom grade of 1 or less Radiological Remission, n (%) - Defined as healing fistula tracts or no active inflammation seen on MRI	48 (84.2) 33 (57.8)
Subtherapeutic Therapeutic Drug Monitoring (All biologic agents) In Remission, n (%) Active Disease, n (%)	18 (56.2) 14 (43.8)

Table 1. Baseline characteristics

57 patients (median age, 40 years (31-54); 52.6% male) with PFCD were included in the study and followed over a median duration of 46.5 months (23.8-72.3). There were a total of 157 individual surgical procedures over the period, 2.75 per patient, most of which (94.2%) were examination under anaesthesia. Antibiotic therapy was dispensed for either perianal sepsis or an actively draining fistula in 26 patients, 2.65 number of courses per patient. The most common antibiotic prescribed was Metronidazole (68.1%), followed by Amoxicillin / Clavulanic acid (27.7%). The median duration of antibiotic therapy was 5 days (5-7) for Metronidazole and 5 days (5-10) for Amoxicillin / Clavulanic acid. There were 56 (98.2%) patients on biologic therapy. The most common biologic agent was Infliximab (75.4%), followed by Adalimumab (19.3%) and Ustekinumab (3.5%). At the time of analysis, 48 patients (84.2%) were in clinical remission and 33 patients (57.8%) were in radiographical remission. In patients treated with infliximab, 37/43 (86%) had therapeutic drug monitoring performed. Amongst these, 30 (81.1%) had subtherapeutic levels (defined as Infliximab level < 10), with 12/30 (40%) of patients having active PFCD.

Conclusion

Across two tertiary IBD centres, management of PFCD is variable and not in keeping with current guidelines. Short courses of antibiotic therapy were used, and the majority of patients had subtherapeutic drug levels when tested. Optimising outcomes for patients with PFCD requires awareness of best practice and a multidisciplinary team approach.

Introduction

Intestinal ultrasound (IUS) has proven to be a valuable tool for accurately detecting intestinal damage and characterizing disease behavior in Crohn’s disease (CD). IUS scoring systems for CD activity have been developed, however all the studies had methodological flaws. Therefore, studies comparing and validating the existing IUS scores in CD patients are required.

Aims & Methods

In this study, we aimed to compare two main existing scores, Bowel Ultrasound Score (BUSS) and International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) in patients with ileal CD using the simplified endoscopic activity score for CD (SES-CD).
An observational cross-sectional study was performed to evaluate the disease activity in adult CD patients with ileal involvement between November 2019 and February 2024. All patients had undergone ileocolonoscopy and IUS, the time interval between the two procedures was lower than 10 days. Receiver operating characteristic (ROC) curve analyses was performed for BUSS and IBUS-SAS to predict SES-CD ≤2 for CD.

Results

Total 56 adult patients with ileal CD were included in the study, 38 patients (67.9%) were male, the median age was 40.5 (IQR 26-46.75) years and the median duration of the disease was 8.4 (IQR, 4.93-10.29) years. In the endoscopically remission (SES-CD ≤2) group; the median BUSS was 2.63 (IQR 2.12-3.45) and the median IBUS-SAS was 14 (IQR, 11.3-18.4), while in the endoscopically active (SES-CD >2) group; the median BUSS was 5.67 (IQR, 3.47-7.76) and the median IBUS-SAS was 49.7 (IQR, 23.3-72.65). The median BUSS and median IBUS-SAS in the endoscopically remission group were significantly lower than those of the endoscopically active group (p< 0.001, for both). The cut-off value for BUSS to determine endoscopic remission (SES-CD ≤2) was 3.9 (AUC: 0.839, 95% CI: 0.737-0.941, sensitivity: 92%, specificity: 73%, p < 0.001), while the cut-off value for IBUS-SAS to establish endoscopic remission (SES-CD ≤2) was 24.4 (AUC: 0.871, 95% CI: 0.780-0.962, sensitivity: 100%, specificity: 73%, p < 0.001).
There was a very high positive correlation between BUSS and IBUS-SAS (r=0.914, p<0.001), a high positive correlation between BUSS and SES-CD (r=0.659, p<0.001), a moderate positive correlation between BUSS and CRP (r=0.577, p<0.001). There was a high positive correlation between IBUS-SAS and SES-CD as well as IBUS-SAS and CRP (r=0.728, p<0.001 and r=0.657, p<0.001 respectively).

Conclusion

In this study, we found that the most accurate cut-off value for BUSS was 3.9 and the most accurate cut-off value for IBUS-SAS was 24.4 in CD patients with endoscopic remission (SES-CD ≤2) group. Also, we have confirmed that both BUSS and IBUS-SAS significantly correlate with endoscopic activity in a real-world cohort.

Introduction

Short bowel syndrome (SBS) is a severe complication of extensive small intestinal resection, most commonly occurring in Crohn’s disease (CD), a chronic inflammatory disorder defined by transmural immune infiltration. Cytokines and chemokines are central mediators in the immune cascade driving intestinal inflammation and tissue damage^1,2. Despite advances in care, no biomarkers currently predict SBS onset or progression to intestinal failure (IF). Profiling systemic cytokine and chemokine signatures may thus offer novel insight into disease trajectory and risk stratification.

Aims & Methods

This study investigates circulating inflammatory mediators in patients with established IF/SBS and CD patients at high risk of progression. A total of 150 patients with CD were enrolled and stratified into five groups based on intestinal function and surgical history: A1, SBS with IF requiring parenteral nutrition (PN) or intravenous fluids; A3, SBS without IF and inactive disease; B, high risk of IF with multiple or extensive resections; C1, low risk for IF with no history of resection; and C2, low risk for IF with prior resection. Serum cytokine and chemokine profiles were quantified at baseline (T0) and after six months (T6) using the human 27-PLEX multiplex immunoassay.

Results

Serum cytokines and chemokines profiling at baseline (T0) and after six months (T6) revealed distinct inflammatory patterns across the study groups. Patients with SBS and IF (group A1) showed persistently elevated levels of IP-10, IL-12, MIP-1α, and G-CSF, reflecting sustained immune activation. Whereas, patients at high risk of IF (group B) displayed increased Eotaxin, bFGF, IL-15, and IL-6, indicative of subclinical inflammation and possible tissue remodelling.
A general reduction in cytokine levels was observed at T6, though anti-inflammatory mediators remained minimally modulated, suggesting ongoing low-grade inflammation. Comparisons between groups highlighted divergent cytokine signatures correlating with disease severity and nutritional support requirements.

Conclusion

These findings suggest that specific circulating cytokines may serve as potential biomarkers for early identification of patients at risk of IF. The differential expression patterns observed across groups support their relevance in stratifying disease severity in CD and SBS. Further large-scale studies are needed to validate these preliminary results and to fully establish their prognostic significance.
Funded by: 2.1 “Rafforzamento e potenziamento della ricerca biomedica del SSN”, finanziato dall’Unione europea – NextGenerationEU, CUP C53C22001140007. 2022 PNRR Project “Changing the future of intestinal failure in intestinal chronic inflammation: towards innovative predictive factors and therapeutic targets” code: PNRR-MAD-2022-12376791.

References

1. Friedrich M, Pohin M, Powrie F. Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease. Immunity. 2019;50(4):992-1006. doi:10.1016/j.immuni.2019.03.017
2. Singh UP, Singh NP, Murphy EA, et al. Chemokine and cytokine levels in inflammatory bowel disease patients. Cytokine. 2016;77:44-49. doi:10.1016/j.cyto.2015.10.008

Introduction

The extent of gastric atrophy(GA) is closely related to the incidence of Intestinal-type gastric cancer (GC). According to the Kimura-Takemoto classification, determining whether the atrophy extends beyond the cardia is key to assess the extent of GA. However, there is significant difficulty in determining whether the cardia is atrophied under endoscopy.

Aims & Methods

This study developed a novel artificial intelligence (AI)-assisted white light endoscopy system for identifying the cardia part and diagnosing cardia atrophy . In this multicenter study, patients undergoing upper gastrointestinal endoscopy at 5 hospitals in China were prospectively included between November 2022 and December 2024. Among them, a total of 895 patients from 2 units were assigned to the training and validation sets (292 with cardia atrophy and 603 without cardia atrophy) to establish a cardia atrophy diagnostic model. 220 patients from our unit (84 with cardia atrophy and 136 without cardia atrophy) were included in the internal test set. Additionally, a total of 354 patients from 3 other units were included in the external test set (106 with cardia atrophy and 248 without cardia atrophy). In the internal and external test sets, 3 senior and 3 junior endoscopists made online diagnoses, comparing the performance differences between physicians with different levles of experience and the AI-assisted cardia atrophy detection system.

Results

This study established a AI-assisted cardia atrophy diagnostic model and tested its diagnostic performance with multicenter image data in internal and external tests. In the internal test dataset, the accuracy, sensitivity, and specificity of the AI-assisted system were 0.927, 0.941, and 0.919, respectively, with a PPV of 0.878, NPV of 0.962, and AUC of 0.967. In the external test dataset, the accuracy, sensitivity, and specificity were 0.918, 0.894, and 0.931 respectively, with a PPV of 0.874, NPV of 0.943, and AUC of 0.953. Further comparison of the diagnostic efficiency of the AI-assisted system with endoscopists of different levels of experience revealed that both in the internal and external test set, the diagnosis accuracy, sensitivity, specificity, PPV, and NPV of the AI-assisted system were all higher than those of senior endoscopists. TheAI-assisted cardia atrophy diagnostic ROC curve area (AUC) was 0.967 and 0.953 in the internal and external test sets, respectively. Heat map analysis further showed a high consistency between theAI-assisted system and endoscopists in cardia atrophy diagnosis.

Conclusion

Our newly developed AI-assisted cardia atrophy diagnostic system shows superior performance in identifying cardia atrophy compared to senior endoscopists, and can be used to guide white light endoscopic judgment and targeted biopsies for cardia atrophy.