Introduction

The STRIDE II guidelines recognize endoscopic healing as one of the main therapeutic targets in Crohn's disease (CD). Nevertheless, transmural healing could reduce the risk of long-term complications. The aim of this study was to assess the risk of long-term complications in CD according to the degree of endoscopic and ultrasound healing.

Aims & Methods

We conducted a prospective study that included all patients with CD in clinical remission who underwent colonoscopy with endoscopic healing (CDEIS <4) and intestinal ultrasound (IUS) within 4 weeks between September 2019 and September 2022. IUS transmural healing was defined by a parietal thickness < 3 mm on all digestive segments (colonic and ileal) without color doppler signal.
The primary endpoint was CD relapse, defined as the need for drug intensification, initiation of corticosteroid therapy, CD-related hospitalization, development of a perianal and luminal fistula or abscess, or the need CD-related bowel surgery. Patients were followed up at least every 6 months for two years.

Results

A total of 93 patients were included, the majority of whom were women (53%) with ileocolonic location (43%). The median disease duration was 12 years (IQR, 4-19) and 71% patients were treated with anti-TNF. Ultrasound transmural healing was observed in 73% (68/93) of patients. After a median follow-up of 22.5 months [IQR, 19.3-23.7] 26% of patients have relapsed. The risk of relapse was significantly higher among patients IUS activity at 6 and 12 months (13% vs. 5% and 24% vs 8 % p = 0.007). In multivariate analysis, the risk of relapse was 3 times higher without IUS transmural healing (HR 3.07 (1.35-9.97); p = 0.007). Among patients with a complete endoscopic healing (CDEIS 0) the relapse rate were also significantly higher among patients with IUS activity compared to those with IUS healing (HR 3.65 (1.06-12.8); p =0.040).

Conclusion

IUS transmural healing was associated with a lower risk of relapse among patients with endoscopic healing and could be considered as a non-invasive therapeutic target in CD.

Introduction

Inflammatory bowel disease (IBD) is a group of chronic inflammatory diseases of the gastrointestinal tract and about 50% of patients develop liver function disorders of different severity in their course. There is unknown cause directly leading to the symptoms of liver damage, one of the suggested causes is impaired mucosal barrier and the associated increased intestinal permeability to bacterial and nutritional antigens and toxins.

Aims & Methods

The aim of the study was to assess the effect of the severity and location of inflammatory lesions in the gastrointestinal tract in the course of IBD on intestinal mucosal barrier disorders and the occurrence of symptoms of liver damage. To assess the degree of mucosal barrier impairment, the intestinal and liver fatty acid-binding proteins (I-FABP and L-FABP) concentrations were assessed, which are sensitive markers of mucosal damage and to assess the degree of liver damage, the fibroblast growth factor (FGF-19) concentrations assessment and laboratory and imaging results. For IBD severity evaluation, the clinical activity scoring indexes and serum tumour necrosis factor alpha (TNF-alpha) concentrations were assessed.
There were 20 children with Ulcerative Colitis (UC, 12 boys, 8 girls, mean age: 16.0 yrs, range: 7.5 – 18) and 20 with Crohn's Disease (CD, 10 boys, 10 girls, mean age: 14.8 yrs, range: 6.3 – 18) and 20 healthy controls enrolled into the study. Serum I-FABP, L-FABP, FGF-19 and TNF-alpha concentrations were assessed at the baseline, before the treatment and after 2 weeks of treatment, using ELISA immunoassays. Statistical analysis was performed with Statistica 13.0 software (TIBCO Software, USA) using Mann-Whitney U test, Wilcoxon signed rank test and Spearman’s correlation rank test.

Results

We found significantly elevated serum I-FABP in active UC group when compared to active CD group and controls (p<0.05), while in inactive UC group and inactive CD group they were comparable to controls (p=NS).
Moreover, serum L-FAPB was significantly increased in active UC group when compared to active CD group and controls (p<0,05) and in inactive UC group when compared to inactive CD group and controls (p<0,05).
When we assessed serum FGF-19 concentrations, we found them significantly increased both in active UC and active CD when comparable to controls (p<0,05) and in inactive UC group when compared to inactive CD group and controls (p<0.05). Additionally, serum FGF-19 concentrations were related to the stage of liver impairment in UC patients.

Conclusion

Increased serum concentrations of I-FABP and L-FABP may be associated to impaired mucosal barrier in IBD. Nevertheless, impaired mucosal barrier may be connected to increased penetration of bacterial and nutritional antigens and toxins and secondary may be related to liver damage. Furthermore, increased serum FGF-19 concentration may be associated with liver damage in the course of IBD in children.

Introduction

While inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), affects people of all sexes, potential disparities in the diagnostic process—such as differences in symptom onset, symptom reporting, and time to diagnosis—have not been systematically investigated in depth to date.

Aims & Methods

This analysis aims to explore potential sex differences in the pre-diagnostic symptom presentation and the diagnostic pathway of IBD, spanning from the onset of first symptoms to the eventual clinical diagnosis. In this interim analysis of a multicenter cross-sectional study, data of 1180 participants with IBD (women: n=770, men: n=410) from 42 recruiting units all over Germany were included. A comprehensive set of demographic data was collected via an online survey, encompassing the following variables: the IBD entity, sex and gender identity, age, the initial symptoms of IBD, the time from symptom onset to first consultation, the time from first consultation to referral, and the time to diagnosis. In addition, the respective physician's sex was documented. Moreover, the distinct disease-related and therapeutic histories have been collected. Inclusion criteria were a minimum age of 18 years and a confirmed diagnosis of UC or CD for a minimum of three months.

Results

No significant sex differences were observed in the median time to initial physician consultation for either CD or UC (CD: women 3 months [IQR: 1–12], men 3 months [IQR: 0.5–10], p=0.567, g=0.1; UC: women 2 months [IQR: 0.8–5], men 1.3 months [IQR: 0.5–4], p=0.091, g=0.1). Similarly, the median time from first consultation to referral did not differ significantly between sexes (CD: women 1.5 months [IQR: 0.5–5], men 1 month [IQR: 0.5–6], p=0.154, g=0.1; UC: women 0.8 months [IQR: 0.3–3], men 0.5 months [IQR: 0.2–1], p=0.113, g=0.2).
However, women experienced significantly longer median time from symptom onset to final IBD diagnosis compared to men (CD: women 12 months [IQR: 5–48], men 6.5 months [IQR: 2.5–24], p=0.002, g=0.3; UC: women 5 months [IQR: 2–14.5], men 3 months [IQR: 1.3–8], p=0.006, g=0.2). The misdiagnosis rate was found to be significantly higher in women with IBD than in men (IBD women: n=311 (40.4%); IBD men: n=141 (34.4%); p=0.044). Furthermore, sex-specific differences in the initial presentation of symptoms were observed. Women with CD were more likely to present with diarrhea (p=0.005, ϕ =0), nausea (p=0.013, ϕ=0), or arthralgia (p=0.012, ϕ =0) compared to CD men. In UC, women were more likely to initially experience fever (p < 0.001, ϕ = 0) or abdominal pain (p = 0.004, ϕ = 0) compared to men.

Conclusion

Despite similar timelines for initial physician contact and referral, women with IBD experienced significantly longer diagnostic delays and higher rates of misdiagnoses than men. Sex-specific differences in initial symptom presentation were observed, suggesting that diagnostic disparities may be partly driven by variations in symptom profiles and their interpretation. These challenges call for a broader, global perspective and increased awareness to improve the overall care of individuals with IBD on an international scale.

Introduction

Currently three JAK inhibitors (JAKi) are licensed for use in UC. Establishing real-world data, via large multicentre cohorts is key in gaining a better understanding of their effectiveness and safety in day to day practice.

Aims & Methods

Our aims were to evaluate the real-world effectiveness and safety of the JAKi; upadacitinib, tofacitinib and filgotinib for the treatment of UC across Scotland, UK. We conducted a retrospective, multicentre, cohort study including data from 14 hospitals in Scotland, UK. Adult patients (>18 years) with a diagnosis of UC or IBDU favouring UC and minimum of 8-weeks follow up post initiation of JAKi for active disease were included. Patients receiving JAKi for indication of acute severe UC were excluded. The primary outcome was treatment persistence of each JAK-i (tofacitinib, upadacitinib, filgotinib) at week 24. Secondary endpoints included un-adjusted comparison of persistence (Kaplan-Meier survival analysis, log-rank test for comparison), predictors of JAKi persistence (multi-variable Cox regression analysis), corticosteroid-free clinical remission, biochemical remission (C-reactive protein ≤5 mg/L) and faecal calprotectin remission (<250 µg/g) at week 8 and 24. Patients who stopped therapy due to lack of efficacy prior to these time points were considered failures. Serious adverse events (SAE) (defined as events leading to to hospitalisation, cessation of drug, disability or death), adverse events (AE) of infection and AE of interest were also documented.

Results

A total of 480 patients (upadacitinib, n=71; tofacitinib, n=208; filgotinib, n=201) had received a JAKi between 2019 (2nd Quarter) and 2023 (4th Quarter) and also fulfilled our inclusion criteria. The median follow-up of the total cohort was 1.4 years (IQR 0.6-2.6 years). The median age and disease duration was 39.0 years (IQR 29.0-52.0 years) and 5.9 years (IQR 2.2-11.1 years), respectively. Cumulative treatment persistence was 83.3%, 76.5% and 80.8% at week 24 in the upadacitinib, tofacitinib and filgotinib cohorts, respectively. There was no significant difference in un-adjusted persistence at week 24 between the three types of JAKi (log-rank, p=0.69). Multi-variable Cox regression revealed that patients with mild (HR 0.5, 95% CI 0.3-0.9, p=0.02) and moderate (HR 0.6, 95% CI 0.4-1.0, p=0.046) clinical disease activity at baseline had a lower risk of treatment cessation, whilst female patients (HR 1.5, 95% CI 1.0-2.2, p=0.03) and current smokers (HR 3.2, 95% CI 1.1-7.4, p=0.02) had a greater risk of treatment cessation. Effectiveness outcomes were similar across the three JAKi cohorts (Table 1). SAEs and AE of infection were lowest in the filgotinib cohort, with a signal towards higher rates of Herpes Zoster with tofacitinib (Table 1).

Table 1. Effectiveness and safety outcomes of ScotJAK cohort.
(PGA, physician's global assessment; pMayo, partial Mayo score; SCCAI, simple clinical colitis acitivity index; MACE, major adverse cardiovascular events; VTE, venous thromboembolism).

Conclusion

We have shown in a large, multi-centre study, encompassing a broad range of hospital practices that all three JAK-i are effective at treating patients with UC in the real-world.

Introduction

The integrity of the intestinal barrier is crucial in preventing bacterial translocation and systemic inflammation, both of which contribute to the progression of advanced chronic liver disease (ACLD). While surrogate biomarkers exist, direct real-time assessment of intestinal barrier function has been challenging. Confocal laser endomicroscopy (CLE) is a high-resolution imaging technique that allows direct visualization of mucosal integrity during endoscopy.

Aims & Methods

The present study aims to determine the prevalence of CLE-detectable barrier dysfunction in ACLD patients, to explore its association with disease severity, and to assess its prognostic significance. In our prospective study, 48 ACLD patients who underwent routine upper gastrointestinal endoscopy between 11/2022 and 04/2024 were examined using CLE (Cellvizio®) in the duodenum following intravenous fluorescein injection (2.5–5 mg). The presence or absence of fluorescein leakage into the intestinal lumen was determined. The presence of leakage in more than three different locations in the duodenum was indicative of intestinal barrier dysfunction. Clinical data including Child-Turcotte-Pugh (CTP) score, MELD score, hepatic venous pressure gradient (HVPG), liver stiffness measurement (LSM), and biomarkers of liver function were recorded. Patients were followed for a median of 13.2 months, with liver-related events (LRE) including first or further decompensation, acute-on-chronic liver failure (ACLF), and liver-related death as endpoints.

Results

Intestinal barrier dysfunction was detected in 52% of patients and was found to be significantly more prevalent in decompensated ACLD compared to compensated ACLD (73% vs. 25%, p=0.021). CLE-based barrier dysfunction correlated with bilirubin (p=0.033) and albumin (p=0.010), but not with HVPG (p=0.314), LSM (p=0.482), or C-reactive protein (p=0.457). Patients exhibiting intestinal barrier dysfunction demonstrated a significantly higher risk of LRE during follow-up (25% vs. 5% at 12 months, 43% vs. 5% at 18 months, log-rank p=0.005). In univariable Cox regression analysis, intestinal barrier dysfunction remained independently associated with LRE (hazard ratio: 2.36, 95% confidence interval: 1.34–84.0, p=0.025). Importantly, the prognostic impact of CLE findings aligned with established risk markers such as MELD and albumin.

Conclusion

CLE provides real-time, high-resolution insight into intestinal barrier integrity in ACLD patients. The strong correlation between CLE-detected barrier dysfunction and adverse clinical outcomes suggests that CLE has the potential to serve as a prognostic instrument for risk stratification. As CLE can be integrated into standard endoscopic procedures, it may provide an accessible and clinically relevant means of assessing intestinal barrier function in routine practice in patients with liver cirrhosis. Further studies in larger cohorts are needed to validate CLE for routine clinical use and to explore therapeutic interventions targeting intestinal barrier dysfunction.

Disclosure

NO CoI to declare

Introduction

Inflammatory bowel disease (IBD) is a complex disease characterized by the dysregulation of host immunity. A key feature is the intestinal activation of T cells with cytotoxic activity and pro-inflammatory cytokine release. Therefore, targeting these pro-inflammatory T cells is a reasonable therapeutic approach. CCR9 is the main activator of gut tropism in the lymphocytes and a promoter of their migration into the lamina propria.
SBR3 is a best-in-class anti-CCR9 monoclonal antibody that effectively depletes CD4⁺ CCR9⁺ T cells in intestinal biopsies and peripheral blood of Crohn’s Disease (CD) and Ulcerative Colitis (UC) patients, which leads to a marked reduction in pro-inflammatory cytokines and restoration of immune homeostasis.
The main objective of this study is to evaluate the translational efficacy of SRB3 in depleting CD4⁺CCR9⁺ T cells in intestinal explants from patients with UC and CD, and to assess its correlation with clinical parameters such as fecal calprotectin levels and current treatments.

Aims & Methods

Intestinal biopsies were collected in routine colonoscopies with inflammatory activity (defined as a Mayo Endoscopic Score <1 in ulcerative colitis and presence of ulcers in CD) from a cohort of IBD patients that included both naïve individuals and those previously treated with biologics, including TNF inhibitors (adalimumab, infliximab) and IL-12/23 antagonists (ustekinumab). Gut explants were cultured and treated ex vivo with SRB3. The frequency of CD4⁺CCR9⁺ T cells and cytokine levels were measured by flow cytometry and multiplex immunoassays. Clinical and demographic parameters from the patient cohort, including smoking habits, type of disease, Montreal Classification, and fecal calprotectin levels (μg/g), were reviewed to evaluate correlations with SRB3 response.

Results

SRB3 efficiently depleted CD4⁺ CCR9⁺ T cells in both naïve patients and those treated with biologic therapies, including anti-TNF agents and IL-12/23 antagonists, indicating robust activity across diverse treatment backgrounds.
Importantly, higher levels of fecal calprotectin showed a statistically significant correlation (p = 0.032) with the extent of CCR9⁺ cell depletion following SRB3 treatment. Given that elevated calprotectin levels are commonly associated with active disease or acute inflammatory flares, this finding suggests that SRB3 is particularly effective in patients with moderate-severe inflammatory activity.

Conclusion

These findings support the broad therapeutic potential of SRB3 in IBD patients, demonstrating efficacy not only in bio-exposed patients but also in those with active disease, where higher calprotectin levels correlate with stronger depletion levels.

Disclosure

Dr. Barreiro and Dr. Conde are both collaborators in a project funded by SunRock Biopharma.