Introduction

The Health Outcome Observatory (H2O) project aims to standardize and facilitate the collection of patient-reported outcomes (PROs) as well as clinical outcomes by a Core Outcome Set (COS) defined for patients with inflammatory bowel disease (IBD).¹ The present study describes preliminary data on the PROMIS^®-10 questionnaire (Patient-Reported Outcomes Measurement Information System) – a generic health-related quality of life measure - in IBD patients.

Aims & Methods

This is a real-world interim analysis of IBD patients included in the H2O project at the Medical University of Vienna, Austria. The variables analyzed were part of the COS. PROMIS^®-10 was evaluated, including Global Physical Health and Global Mental Health scores. Higher scores indicate better health and a score between 40 and 59 was defined as normal range. A descriptive analysis and a correlation analysis, including sex, age, age at diagnosis, disease duration, IBD_Disk_managing_defecation_day and night, IBD_urge, PRO-2 for CD (number of liquid or very soft stools and abdominal pain score) and UC (rectal bleeding score and stool frequency score) were performed.

Results

691 patients (46% females) were included in the analysis. 460 were diagnosed with Crohn’s disease (CD), 220 with ulcerative colitis (UC), and 11 with IBD unclassified (IBDU). The PROMIS scores were similar in CD and UC. The mean PROMIS Global Physical Health score was 41.5 (SD 5.3) in CD and 41.9 (SD 4.5) in UC, respectively. The mean PROMIS Global Mental score was 46.9 (SD 8.8) in CD and 48.4 (SD 8.3) in UC. 223 patients had a PROMIS Global Physical Health score < 40, and no patient had a score > 59. 89 patients had a PROMIS Global Mental Health score < 40, and 32 patients had a score > 59. The PROMIS Global Physical Health score correlated with the Mental score (r=0.23; p<0.001), sex (male r=0.13; p=0.003), PRO-2 for CD number of liquid or very soft stools (r=-0.11; p=0.01) and abdominal pain score (r=0.14; p=0.002). The PROMIS Global Mental Health score correlated with sex (male r=0.13; p=0.004), the IBD_Disk_managing_defecation_day (r=-0.32; p<001) and night (r=-0.31; p<0.001), IBD_urge (r=-0.33; p<0.001), PRO-2 for CD number of liquid or very soft stools (r=-0.34; p<0.001) and abdominal pain score (r=-0.49; p<0.001), and PRO-2 for UC rectal bleeding score (r=-0.13; p=0.004) and stool frequency score (r=-0.35; p<0.001).

Conclusion

About one third of the patients had a PROMIS Global Physical Health score below the normal range. The majority of the IBD patients had a PROMIS Global Mental Health score within the normal range, which correlated with the severity of gastrointestinal symptoms, including urgency and incontinence.

References

¹Fierens L, Carney N, Novacek G, van der Woude CJ, Siegmund B, Casellas F, et al. A Core Outcome Set for Inflammatory Bowel Diseases: Development and Recommendations for Implementation in Clinical Practice Through an International Multi-stakeholder Consensus Process. J Crohns Colitis. 2024 Oct 15;18(10):1583-1595.

Disclosure

H2O has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 945345. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and Trial Nation and JDRF. www.ihi.europa.eu DISCLAIMER: this poster reflects only the author’s view. Neither IMI, nor EFPIA, nor the European Commission, nor the JU are liable for any use that may be made of the information it contains.

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

Acute severe ulcerative colitis (ASUC) is a potentially life-threatening emergency that requires timely management. Intravenous corticosteroids are the first line therapy, but around 30% of patients fail to respond. Rescue therapy is effective in reducing short-term colectomy rates but its impact on disease course in the medium/long-term is not well characterized.

Aims & Methods

We aimed to assess if non-response to corticoids (and subsequent need for rescue therapy) in patients admitted with a first episode of ASUC is associated with worse disease-related outcomes in the long-term.
We conducted a retrospective study of all patients admitted with ASUC in the Gastroenterology department of a Portuguese tertiary center between 2018-2024. ASUC diagnosis was established according to Truelove and Witts’ criteria. Response to intravenous corticoids was defined as discharge without need for rescue therapy and/or colectomy. Patients with a previous admission for ASUC before the study period were excluded.
Patient files were reviewed and demographic, clinical, laboratory and endoscopic data was collected regarding the admission for ASUC and subsequent follow-up. Considered disease-related outcomes were need for switch of maintenance therapy, need for readmission and need for colectomy. Subanalyses were performed according to response to corticoid therapy. Statistical analysis was done using Stata version 12.1.

Results

A total of 35 patients hospitalized with a first episode of ASUC were included, 51.4% (n=18) male, median age at admission was 38 years [IQR 27-51]. Roughly half the patients had pancolitis at diagnosis (51.4%, n=18). Median disease duration was 9 months [IQR 0-26] and 22.9% (n=8) had previous exposure to biologic therapy. In 34.3% (n=12), ASUC was the initial presentation of UC. Median follow-up was 30 months [IQR 12-51].
Response to corticosteroid therapy was observed in 57.1% (20/35). All the steroid-refractory patients (15/35, 42,9%) responded to rescue therapy (Infliximab n=11; Tacrolimus n=3; Tofacitinib n=1) and avoided colectomy during the hospitalization.
Baseline characteristics were identical between steroid-responsive and steroid-refractory patients, except for a lower median age in corticoid refractory patients (29 years vs 48 years, p=0.02).
Survival analysis was performed and no differences between steroid-responsive and steroid-refractory patients were observed in need for switch of maintenance therapy [during first year (p=0,28) and during complete follow-up (p=0,54)] , need for readmission [during first year (p=0,55) and during complete follow-up (p=0,54)] or need for colectomy [during first year (p=0,09) and during complete follow-up (p=0,79)].

Conclusion

In our cohort of patients with a first episode of ASUC, with the current therapeutic paradigm, patients with steroid refractoriness had similar outcomes as corticosteroid responders. These results suggest that effective and timely therapy can change the natural history of ASUC.

References

1. Festa S, Scribano ML, Pugliese D, Bezzio C, Principi M, Ribaldone DG, Allocca M, Mocci G, Bodini G, Spagnuolo R, Vernia P, Mazzuoli S, Costa F, Barberio B, Cosintino R, Zerboni G, Aratari A, Armuzzi A, Papi C. Long-term outcomes of acute severe ulcerative colitis in the rescue therapy era: A multicentre cohort study. United European Gastroenterol J. 2021 May;9(4):507-516. doi: 10.1177/2050640620977405. Epub 2021 Feb 16. PMID: 33259773; PMCID: PMC8259429.
2. Zafer M, Zhang H, Dwadasi S, Goens D, Paknikar R, Dalal S, Cohen RD, Pekow J, Rubin DT, Sakuraba A, Micic D. A Clinical Predictive Model for One-year Colectomy in Adults Hospitalized for Severe Ulcerative Colitis. Crohns Colitis 360. 2021 Dec 21;4(1):otab082. doi: 10.1093/crocol/otab082. PMID: 36777555; PMCID: PMC9802419.

Introduction

Approximately 50% of patients with Ulcerative Colitis (UC) suffer from daily symptoms of faecal urgency, significantly impacting their quality of life¹. Treatment in quiescent disease is challenging and the first line treatment, loperamide, is often used with caution due to the side effect of constipation.
Enterosorbents such as Enterosgel provide a potential alternative treatment. Enterosgel is thought to work through the adsorption of small molecules in the gastrointestinal (GI) tract, with minimal or no systemic absorption and metabolism², without causing constipation. Enterosgel has shown clinical effectiveness in reducing urgency in patients with diarrhoea predominant irritable bowel syndrome (IBS-D), suggesting potential therapeutic value in patients with UC³, however the mechanism by which this may occur is unknown.

Aims & Methods

This study aimed to evaluate the in vitro adsorption capacity of Enterosgel for three key inflammatory mediators implicated in UC pathogenesis (IL-1β, MMP9 and TNF-α) to explore its potential as a therapeutic option in this patient group.
Three experimental paradigms were performed by diluting recombinant cytokines and enzymes in water-based Enterosgel solutions. After incubation, gel-free supernatants were harvested to analyse residual levels of metabolite via ELISA to identify the quantity of adsorption by Enterosgel. Conditions were conducted with different:

1. Incubation times (15,30,60,120 min)
2. Metabolite concentrations (5 concentrations ranging from 0 - 3000pg/mL)
3. Gel concentrations (0.056, 0.1125, 0.225g/mL)

Results

Enterosgel demonstrated measurable concentration-dependent adsorption of IL-1β, MMP9 and TNF-α with higher analyte input concentrations resulting in greater absolute adsorption. However for TNF-α adsorption saturated at 1000pg/mL, indicating that Enterosgel may not fully adsorb analytes at levels simulating extreme luminal inflammation. Charcoal consistently resulted in lower residual concentrations, although this did not reach statistical significance on permutation testing (p = 0.14).
In time dependent analysis, Enterosgel induced a rapid initial reduction in cytokine levels within 15 minutes, (IL-1β: 98.7%, MMP9: 99.4%, TNF-α: 95.8% adsorbed) with a plateau by 120 minutes (IL-1β: r²=0.74, MMP9: r²=0.64, TNF-α: r²=0.45). In contrast, charcoal demonstrated a near-linear monotonic decline with a slightly greater concentration adsorbed by 120 minutes (IL-1β: 99.9% vs. 99.8%; MMP9: 99.9% vs. 99.1%; TNF-α: 97.2 vs. 96.3%). Increasing gel concentrations improved adsorption efficiency; however, at the highest gel concentration small amounts of residual cytokines remained (IL-1β: 0.25%, MMP9: 0.28%, TNF-α: 3.5%). Doubling of gel concentration led to an average 30% decrease in residual cytokines.

Conclusion

Our findings suggest that Enterosgel demonstrates excellent adsorption of three key pro-inflammatory cytokines relevant to UC, with the greatest reduction at 1 hour and the highest gel concentration—though less than that achieved by charcoal. Evidence of saturation at high analyte levels suggests a limit to Enterosgel’s binding capacity under conditions simulating severe inflammation. These results highlight Enterosgel's clinical potential, however further validation with biological replicates and clinical studies assessing urgency in treated UC is required.

References

(1) Theresa Hunter Gibble, April N. Naegeli, Michael Grabner, Keith Isenberg, Mingyang Shan, et al. Identification of inadequate responders to advanced therapy among commercially-insured adult patients with Crohn’s disease and ulcerative colitis in the United States. 2023; 63 (23): 10.1186/s12876-023-02675-w.
(2) Howell CA, Mikhalovsky SV, Markaryan EN, Khovanov AV. Investigation of the adsorption capacity of the enterosorbent Enterosgel for a range of bacterial toxins, bile acids and pharmaceutical drugs. Scientific Reports. 2019; 9 (1): 10.1038/s41598-019-42176-z.
(3) Howell CA, Kemppinen A, Allgar V, Dodd M, Knowles CH, Mclaughlin J, et al. Double-blinded randomised placebo controlled trial of enterosgel (polymethylsiloxane polyhydrate) for the treatment of IBS with diarrhoea (IBS-D). BMJ; 2022.
(4) Shane O'Sullivan, John F Gilmer, Carols Medina. Matrix Metalloproteinases in Inflammatory Bowel Disease: An Update. Mediators of Inflammation. 2015; 2015 (1): 10.1155/2015/964131.
(5) Qingdong Guan JZ. Recent Advances: The Imbalance of Cytokines in the Pathogenesis of Inflammatory Bowel Disease. Mediators of Inflammation. 2017; 2017 (1): 10.1155/2017/4810258.