Introduction

Inflammatory bowel disease (IBD) represents a group of chronic inflammatory disorders of the gastrointestinal tract. While the hallmark features of IBD involve inflammation and damage to the digestive system, the impact of the disease often extends beyond the gut, manifesting as a spectrum of extraintestinal manifestations (EIM), affecting various organs and contributing to the complexity and heterogeneity of IBD.

Aims & Methods

The aim of this study was to assess the impact of EIM in IBD on disease course. We conducted a retrospective, descriptive and comparative study including patients hospitalized for IBD over a 9-year period [January 2011-January 2020]. Patients with less than 2 years of follow-up were excluded. Clinico-biological data, disease severity, and long-term outcomes (surgery and disease course) were collected. Data were entered and analyzed via SPSS 26 software.

Results

We included 225 men and 227 women. We enrolled 341 patients diagnosed with Crohn's disease (CD) and 111 patients with ulcerative colitis (UC). The mean age at diagnosis was 36.15 ± 12.74 years. One-hundred and sixty-five patients (36.4%) had EIM with respectively: rheumatological manifestations (n=144), dermatological manifestations (n=26), ocular manifestations (n=17) and hepatic manifestations (n=8). We noticed a significant association of EIM with male gender (56.3% vs 45.9%; p=0.03). Rheumatological EIM were associated with a significant older age at disease onset (36.7 years vs 32.8 years; p=0.003). No significant association was noted between EIM with neither family history of IBD nor the type of IBD (p=0.33 and p=0.3 respectively). In case of CD, we noted a higher frequency of ileal involvement in patients with EIM, without a significant difference (61.4% vs 51.4%; p=0.07). No association was noted between EIM with neither fistulising behaviour nor with extended ileal disease nor with upper gastrointestinal tract involvement (p=0.1; p=0.5 and p=0.5 respectively). In case of UC, no association was noted between EIM and an extensive disease (p=0.7). As for treatment, EIM had no impact on corticosteroids’ use or immunosuppressive treatment (p=0.36 and p= 0.08), but was associated with a significant higher use of anti-TNF therapy (83.4% vs 27.2%; p=0.01). Response to corticosteroids and anti-TNF therapy was similar whether with or without EIM (p= 0.36 and p=0.24 respectively). In the sub-group of ocular EIM, we noted a higher failure of immunosuppressive treatment (70% vs 36.6%; p=0.04). We noted that EIM was associated with a rarer urge to surgical treatment (35.7% vs 44.9%;p=0.05) with a significant longer timeframe to surgery (47.7 months vs 27,2 months; p=0.03). The mean number of years of active disease was significantly higher in patients with EIM (3.3 vs 2.5; p=0.002) with a higher number of flare-ups (p=0.009) and hospitalizations (p<0.001), reflecting a better disease course in patients without EIM.

Conclusion

In our study, EIM were associated with an overall more severe disease course in IBD, thus, emphasizing the importance of comprehensive assessment and management strategies tailored to address both intestinal and extra-intestinal manifestations in the holistic care of IBD patients.

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.

Introduction

Upadacitinib has shown to be more effective than placebo for treating extraintestinal manifestations (EIM) in post-hoc analyses. However, real-world data on the effectiveness of upadacitinib in patients with inflammatory bowel disease (IBD) and EIMs are lacking.

Aims & Methods

A multicenter, retrospective and observational study was conducted at 19 Spanish hospitals. Patients with IBD and active EIMs when initiating upadacitinib were eligible. The primary outcome was EIM improvement at weeks 8-12. The EIM assessment was based on the physician's subjective evaluation and categorized into clinical remission, partial response, nonresponse and worsening. EIM improvement was defined as either clinical remission or partial response. Axial arthropathy, peripheral arthropathy, pyoderma gangrenosum, erythema nodosum, sweet syndrome, aphthous stomatitis, uveitis, episcleritis, primary sclerosing cholangitis and bronchiectasis were considered. In patient experiencing >1 EIM, all had to be resolved or improved to be considered. If not, the worst outcome was recorded. Patients’ visits were scheduled at weeks 0, 8-12, and 6 months. Multivariate analysis was performed to find factors associated with EIM improvement at w8-12.

Results

A total of 160 patients were included, 120 patients with Crohn’s Disease (75.6%), 90 females (56.3%) with a median age of 46.6 years (IQR 37.9-56.7). Upadacitinib was initiated in one hundred twenty-six (78.8%) patients due to EIMs and luminal activity and 35 patients (21.3%) exclusively due to EIMs. All patients were bio-experienced with 84 patients previously treated with ≥3 biologics (52.5%). Baseline EIMs assessment was for at least 1 EIM in 107 patients (66.9%), 42 patients presented 2 EIMs (26.3%) while 11 patients (6.9%) experienced ≥ 3 EIMs.
At w8-12, 99 patients (61.9%) achieved EIM improvement, 40 patients (25 %) clinical remission, 58 patients (36.9%) partial response, 58 patients (36.5 %) nonresponse and worsening in 3 patients. Patients initiating Upadacitinib due to exclusively active EIMs was associated with EIM improvement at weeks 8-12 (OR 2.99 95% CI 1.06-8.42; p=0.04). IBD clinical remission at w8-12 was achieved in 75 patients (61%).
Evaluation at 6 months was available for 103 patients, 73 patients (70.9%) presented EIM improvement, 41 patients (39.8%) clinical remission, 32 patients (31.1%) partial response, 20 patients (19.4%) nonresponse and 10 patients (9.7%) worsening. IBD clinical remission at 6 months was achieved in 51 patients (62.2%).
During the follow-up, Upadacitinib was ceased in 27 patients (16.9%). Adverse events were detected in 39 patients (24.3%) and 7 patients (4.4%) experienced worsening of previous inactive EIMs.

Conclusion

Upadacitinib was highly effective in the short term for treating bio-experienced patients with active EIMs, particularly for patients without luminal activity

Disclosure

No conflict

Introduction

Perianal fistulas occur in up to 30% of patients with Crohn’s disease (pfCD) and frequently require a combined medical and surgical treatment approach. Hyperbaric Oxygen Therapy (HBOT) has previously shown benefit in treatment-refractory pfCD.

Aims & Methods

In this pilot study, we aim to assess the feasibility of surgical fistula closure 4 weeks after HBOT, and efficacy of combining surgical closure and 8 weeks HBOT.
Patients with complex pfCD refractory to at least 6 months of anti-TNF therapy were included in this study. All patients received a seton prior to starting treatment with 40 sessions (8 weeks) of HBOT (each lasting 110 minutes, with 5-minute air breaks) with 100% oxygen at 2.4 atmosphere. At week 4 the seton was removed, and surgical closure of the internal fistula opening was attempted. All patients continued stable dose of medical treatment during the study. Response was assessed by the fistula drainage assessment (FDA) and the perianal disease activity index (PDAI) at week 9, 26 and 52, and by pelvic MRI at week 9 and 26. MRI response was defined as a decrease of 2 points in MAGNIFI-CD score, MRI remission as a MAGNIFI-CD ≤6. (Serious) Adverse Events (AE) were reported for 52 weeks. Univariate logistical regression was used to explore potential variates associated with PDAI response (≤4) at week 26.

Results

Ten patients completed treatment and were analyzed (Table 1). All patients completed HBOT and underwent a technically successful surgical procedure at week 4. No proctitis was encountered at week 4 during examination under anesthesia. PDAI response was achieved by 30%, 60%, 58% at week 9, 26 and 52, respectively. FDA response/remission was achieved in 50%/20%, 80%/40% and 80%/50% of patients at week 9, 26 and 52, respectively. MRI response/remission was achieved in 60%/10% and 60%/20% of patients at week 9 and 26, respectively. No significant parameters were associated with PDAI response at week 26 in univariate logistical regression. (S)AEs included one patient with a potential oxygen toxicity seizure without long term effects, and one patient reported claustrophobia, no new AEs were reported.

Table 1 Patient and fistula characteristics (n=10)

Conclusion

HBOT is feasible in combination with surgical therapy in patients with complex pfCD refractory to anti-TNF therapy. Patients had long-lasting benefit of the combined treatment approach. Further translational data are currently analyzed to clarify mechanisms of action and to explore potential biomarkers for therapy response.

Disclosure

LM, KB, JT and RvH have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this abstract. JS is President-elect of the European Society of Gastrointestinal and Abdominal Radiology. GD has served as consultant for AbbVie, Astrazeneca, Alimentiv, Bristol-Myers Squibb, Boehringer Ingelheim, Celltrion, Cosmo, Eli Lilly, Galapagos, GSK, Johnson and Johnson, Takeda, Pfizer Inc, Polpharma, Prometheus Biosciences, Tillotts and Ventyx; received speaker fees from AbbVie, Boehringer Ingelheim, Celltrion, Eli Lilly, Johnson and Johnson, Takeda, Pfizer Inc and Tillotts. CB has received grants from Boehringer Ingelheim and Roche; speakers honoraria from AbbVie, Janssen, Galapagos, Takeda, and Tillotts. KG has received grants from Pfizer Inc, Celltrion and Galapagos; consultancy fees from AbbVie, Arena Pharmaceuticals, Galapagos, Gilead, Immunic Therapeutics, Janssen Pharmaceuticals, Novartis, Pfizer Inc., Samsung Bioepis and Takeda and speaker’s honoraria from Celltrion, Ferring, Janssen Pharmaceuticals, Novartis, Pfizer Inc, Samsung Bioepis, Takeda and Tillotts.

Introduction

Difficult-to-treat Crohn’s disease (CD), as defined by the International Organization for the Study of IBD (IOIBD), encompasses patients with persistent disease activity despite advanced therapies, complex phenotypes (e.g., penetrating complications), or post-surgical recurrence. Upadacitinib, a selective JAK1 inhibitor, has demonstrated efficacy in Western populations, yet data in Asian cohorts remain sparse. This study evaluates the effectiveness and safety of standardized induction regimen of upadacitinib (45mg qd) in Asian patients meeting IOIBD criteria for difficult-to-treat CD.

Aims & Methods

To assess the efficacy and safety of upadacitinib in Asian patients with difficult-to-treat CD, providing evidence for clinical decision-making, a retrospective, multicenter study was conducted from 8 Chinese tertiary centers (January 2023–January 2025) on difficult-to-treat Crohn’s disease patients who met IOIBD criteria. All patients received upadacitinib 45mg qd for 12 weeks. Clinical outcomes were assessed using the Crohn's Disease Activity Index (CDAI), with the primary outcome being clinical remission (CDAI <150) and the secondary outcome being clinical response (CDAI reduction ≥70) at week 12. Adverse events (AEs) were systematically recorded.

Results

We finally collected 151 patients who met IOIBD criteria(Table1). Among them, 147 patients presented failure of ≥2 biologics with distinct mechanisms, 3 patients had complex perianal disease and 1 patient had postoperative recurrence. The mean disease duration of these patients was 7.6 years (SD 4.5 years). At week 12, 71 patients (47.0%) achieved clinical remission, 66 patients (43.7%) showed clinical response, and 14 patients (9.3%) were non-responders. Adverse events occurred in 40 patients (26.5%): acne (n=13), anemia (n=13), leukopenia (n=3), fever (n=4), urinary tract infection (n=2), herpes zoster (n=2), folliculitis (n=1), amenorrhea (n=1), elevated creatine phosphokinase (n=1), and mediastinal tuberculosis (n=1). Most AEs were mild and resolved with oral medications.

Table1. Baseline Characteristics of Patients with Difficult-to-Treat CD Treated with UPA

Conclusion

This is the largest Asian cohort study of upadacitinib for difficult-to-treat CD. The drug demonstrated robust efficacy and a favorable safety profile. Notably, tuberculosis reactivation was rare. Standard dosing showed comparable effectiveness and tolerability to European data, underscoring upadacitinib as a strong therapeutic option in Asian populations.

References

1. Parigi TL, D'Amico F, Abreu MT, et al. Difficult-to-treat inflammatory bowel disease: results from an international consensus meeting. Lancet Gastroenterol Hepatol. 2023;8(9):853-859. doi:10.1016/S2468-1253(23)00154-1
2. Parigi TL, Massimino L, Carini A, et al. Prevalence, Characteristics, Management, and Outcomes of Difficult-to-Treat Inflammatory Bowel Disease. J Crohns Colitis. 2025;19(3):jjae145. doi:10.1093/ecco-jcc/jjae145
3. Bezzio C, Franchellucci G, Savarino EV, et al. Upadacitinib in Patients With Difficult-to-Treat Crohn's Disease [published correction appears in Crohns Colitis 360. 2025 Mar 25;7(1):otaf022. doi: 10.1093/crocol/otaf022.]. Crohns Colitis 360. 2024;6(4):otae060. Published 2024 Oct 24. doi:10.1093/crocol/otae060
4. Devi J, Xu A, Stone M, et al. Real-World Effectiveness and Safety of Upadacitinib in Crohn's Disease: A Multicenter Study. Clin Gastroenterol Hepatol. Published online March 8, 2025. doi:10.1016/j.cgh.2025.01.012