Introduction

Endoscopic assessment is a crucial part of the management of Ulcerative Colitis (UC). The DUBLIN score (DS) has the advantage of assessing both disease activity and extent. The aim of our study was to evaluate the performance of the DS compared to the UCEIS.

Aims & Methods

This is a retrospective study, among patients with UC. Clinico-biological and evolutionary data were collected. We calculated the UCEIS endoscopic score, the Nancy histological index and the DS as a product of the Mayo endoscopic score [0-3] and the disease extent [E1‐E3].

Results

Fifty patients were enrolled with a mean age of 49.1 years [11-83] and a sex ratio M/F of 1.94. The DS showed a statistically significant correlation with both the UCEIS score [r=0.913, p<0.0001] and the Nancy index [r=0.857, p<0.0001]. Regarding biological parameters, there was a significant positive correlation between DS and CRP [r=0.660, p<0.0001] and a weak negative correlation between DS and both albumin [r= -0.575, p<0.0001] and hemoglobin [r=-0.443, p=0.001]. The DS and UCEIS were significantly associated with the occurrence of disease extension (p<0.0001), the need for colectomy (p<0.0001), as well as the need for immunomodulators (p=0.034 and 0.008 respectively). Both scores were not associated with the need for biotherapy (p=0.2 and 0.194 respectively). During follow-up, twenty patients (40%) were in therapeutic failure. When analyzing, the AUROC in predicting the occurrence of treatment failure in UC was 0.913 [95% CI 0.831–0.996] for DS and 0.924 [95% CI 0.846–1] for UCEIS.

Conclusion

Based on our study, although the DUBLIN score was correlated with inflammatory markers as well as clinical and histological data, it did not show superior performances to the UCEIS.

Introduction

Malnutrition and weight loss are well-recognized complications of Crohn disease (CD), however nutritional routine assessment is not commonly performed, resulting in under-detection of both malnutrition and nutrient deficiencies. In fact, a number of nutrition screening tools are available including the Nutritional Risk Index (NRI).
The aim of this study was to assess the nutritional status using the NRI and to investigate the associated factors to malnutrition during CD.

Aims & Methods

We conducted a retrospective single-center study, including patients followed for CD over a 7-year period [2014 - 2021]. Malnutrition risk was estimated based on the NRI calculated at first presentation with the following formula: NRI = (1.519 × serum albumin (g/L) + 41.7× (present weight/usual weight).
Nutrition status of patients was categorized into four groups: NRI>100: no risk group, NRI= 97.5–100: mild risk, NRI= 83.5–97.5: moderate risk, and NRI< 83.5: severe risk group of malnurition. Radiologic sarcopenia was assessed by calculating the total psoas area index.

Results

In total, 50 patients were enrolled with a mean age of 44.3 years, a median disease duration of 106 months and a sex ratio M/F of 3.16.
Based on NRI, 11/50 (22%) patients had normal nutritional status, 27/50 (54%) mild-moderate risk of malnutriton and 12/50 (24%) had severe malnutrition.
In the univariate study, severe malnutrition risk was associated with the presence of anemia (p=0.002), thrombocytosis (p=0.05), hypocholesterolemia (p=0.024), the presence of radiologic sarcopenia (p=0.05), extensive ileal involvement of more than 50 cm (p=0.014), the occurrence of complications such as intra-abdominal collection (p=0.001) and thromboembolic complications (p=0.05). Regarding, patients who underwent surgical treatment, the occurrence of postoperative complications and extensive small bowl resection were factors associated with severe malnutrition with a p-value of 0.02 and 0.025 respectively.
On multivariate regression analysis, severe malnutrition risk was a predictive factor of developing intra-abdominal abscess (OR 10.5 95% CI 2.22-49.51), p=0.003).

Conclusion

Patients with Crohn’s disease have a high incidence of nutritional risk and malnutrition witch was associated with severe course of CD. Nutritional Risk Index is a simple, validated and reproducible tool to identify patients at increased risk of malnutrition allowing adapted nutritional support.

Introduction

Inflammatory bowel diseases (IBD) are systemic disorders that may be associated with extraintestinal manifestations in up to 40% of patients. Recognizing the recurrent emergence of these manifestations in IBD, with a particular emphasis on rheumatological aspect, becomes a pivotal focal point for a holistic therapeutic approach.

Aims & Methods

The aim of this study was to evaluate the impact of ankylosing spondylitis in IBD on disease course. We conducted a retrospective and comparative study, including patients followed for IBD over an 8-year period [2014 - 2022]. Clinico-biological data, disease severity, and long-term outcomes (surgery and disease course) were collected. IBD patients with ankylosing spondylitis (group1) and patients without (group2) were compared. Data were entered and analyzed via SPSS 26 software.

Results

One-hundred IBD patients were enrolled with a sex ratio of M/F=2.44 and a mean age of disease diagnose of 37.26 ± 13.46 years. Eighteen patients had ankylosing spondylitis (18%). The two groups were comparable in terms of age at disease onset, gender, smoking status and family history of IBD (p=0.65; p=0.9, p=1 and 0.1 respectively). In Crohn's disease, there was no difference between the two groups regarding the extent of the disease (p=0.71), the presence of upper gastro-intestinal tract involvement (p=0.11) and perineal manifestations (p=0.7). Inflammatory, structuring, and penetrating phenotypes were also comparable between the two groups (p=0.67; p=0.3; p=1 respectively). However, the occurrence of acute intestinal obstruction was significantly more common in ankylosing spondylitis patients (G1:54% vs. G2:10%; p=0.004). As for ulcerative colitis, extensive presentation (G1:28% vs. G2:41%; p=0.66) and the occurrence of disease extension during follow-up was comparable between the two groups (p=0.78). None of the patients with or without rheumatological involvement had any dermatological or ophthalmological involvement related to IBD, but there was a more significant prevalence of hepatic manifestations in ankylosing spondylitis group (G1:16% vs. G2:2%, p=0.01). The mean number of flare-ups was not significantly different between the two groups (G1:3.21±1.47 vs. G2:2.53±1.4; p=0.06). Regarding treatment, recourse to methotrexate (G1:16% vs. G2:2%; p=0.01) and the use of anti-TNF agents (G1:77% vs. G2:22%; p<0.001) was more frequent in group 1, with no difference in the occurrence of adverse events (p=1), the use of corticosteroids (p=0.22) or azathioprine (p=0.1). Surgical treatment was more frequently indicated in ankylosing spondylitis patients (G1:51% vs. G2:30%; p=0.06). Post-operative relapse of Crohn's disease was comparable between the two groups (p=1).

Conclusion

In our study, rheumatological involvement was not likely responsible of a more severe clinical phenotype of IBD.

Introduction

Regulatory guidance recommends the endoscopy subscore as the index to assess the endoscopic component of the primary endpoint in ulcerative colitis (UC) trials¹. Inter-reader variability in assessments may impact the reliability of trial results^2,3. Currently, there is no metric in place to assess the certainty by which a reader is assigning an endoscopy subscore. Machine learning (ML) provides an opportunity to assess the endoscopy subscore and provide a measurement of its certainty in a standardized manner. Artificial Intelligence Assessment of Endoscopic Severity (AI-ES) accurately assesses the endoscopy subscore⁴. The objective of this study is to evaluate the calibration of AI-ES - how well its predicted probabilities reflect true likelihoods - to assess the reliability of its measurement of certainty in endoscopy subscore assessments in UC trials.

Aims & Methods

AI-ES is a deep learning algorithm that assesses the endoscopy subscore in UC endoscopic videos. AI-ES measures probability for the four ordinal endoscopy subscore classes. The endoscopy subscore with the highest probability is assigned as the final score by AI-ES. We assessed calibration on a holdout test set of 639 videos (~25%) from the Phase 3 induction trial for mirikizumab in UC (NCT03518086). Videos had a 2+1 centrally read endoscopy subscore, randomly selected from week 0 and 12 with a distribution of endoscopic severity similar to the overall study population. Calibration plots were generated across endoscopy subscore classes with probabilities grouped into septiles (~100 videos per group) for primary analysis and deciles for confirmation. Brier scores, ranging from 0 (perfect calibration) to 1 (worst calibration), were calculated, with values <0.25 considered informative⁵.

Results

AI-ES demonstrated strong calibration, with Brier scores below <0.25 for each endoscopy subscore (0: 0.037, 1: 0.082, 2: 0.162, 3: 0.112). The Brier score for evaluation of endoscopic improvement (0,1 vs 2,3) also showed excellent calibration (0.066). Findings were consistent when assessing probabilities by deciles.

Conclusion

Whereas data on the certainty of human readers in endoscopy subscore assessments are elusive, AI-ES is calibrated across all endoscopy subscore classes, providing reliable data on score probabilities. This novel measurement of certainty by AI-ES added to the score assessment may enable novel AI-based multi-reader or consensus workflows in trials, potentially improving the reliability of UC endpoint assessments.

References

1. Food and Drug Administration. Ulcerative Colitis: Developing Drugs for Treatment. Draft Guidance for Industry. April 2022.
2. Hashash JG, Yu Ci Ng F, Farraye FA, Wang Y, Colucci DR, Baxi S, Muneer S, Reddan M, Shingru P, Melmed GY. Inter- and Intraobserver Variability on Endoscopic Scoring Systems in Crohn's Disease and Ulcerative Colitis: A Systematic Review and Meta-Analysis. Inflamm Bowel Dis. 2024 Nov 4;30(11):2217-2226.
3. Wils P, Jairath V, Sands BE, Magro F, Reinisch W, Rubin D, Danese S, Baumann C, Peyrin-Biroulet L. Comparison of treatment effect between phase 2 and phase 3 trials in patients with inflammatory bowel disease. United European Gastroenterol J. 2023 Oct;11(8):797-806.
4. Battioui C, Brodskiy P, Gottlieb K, Haft-Javaherian M, Eastman W, Lehrer J, Yu E, Onken D, Thomason D, Colucci D, Reinisch W, Baxi S. DOP078 Machine learning assessment of endoscopic severity in Ulcerative Colitis trials: Model evaluation against the 2 + 1 reference standard. Journal of Crohn's and Colitis. 2025 Jan;19(1):229-230.
5. Steyerberg EW, Vickers AJ, Cook NR, Gerds T, Gonen M, Obuchowski N, Pencina MJ, Kattan MW. Assessing the performance of prediction models: a framework for traditional and novel measures. Epidemiology. 2010 Jan;21(1):128-38.

Disclosure

CB, KG, WE, and DO are employees of Eli Lilly and may hold stock or stock options in Eli Lilly.
PB, MH, JL, EY, DT, DC, and SB are employees of Iterative Health and may hold stock or stock options in Iterative Health.
WR has served as a speaker for AbbVie, Celltrion, Ferring, Janssen, Galapagos Medice, MSD, Roche, Pfizer, Sobi, Takeda, as a consultant for AbbVie, Amgen, AOP Orphan, Boehringer Ingelheim, Bristol Myers Squibb, Calyx, Celltrion, Eli Lilly, Galapagos, Gilead, Index Pharma, Janssen, Medahead, Microbiotica, Pfizer, Teva, Takeda; as an advisory board member for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Galapagos, Janssen, Pfizer, Teva and has received research funding from AbbVie, Janssen, Sandoz, Sanofi, Takeda.

Introduction

The molecular pathways for the development of ulcerative colitis (UC) are unclear. The purpose of the work is to study the molecular interactions of the apoptotic pathway in patients with UC.

Aims & Methods

The study was prospective comparative cohort with parallel design and included 65 patients (range from 22 to 35 years, 24 men and 41 women) with left-sided UC, mild and moderate activity (Truelove - Witts’ criteria, Mayo score). The induction of UC remission assumed the acceptance of mesalazine 3 to 4 g/day p.o. and rectally 1 to 2 g/day, the duration of therapy was 4.6 years. The control group
included 30 healthy individuals. The separation of individual proteins of colon mucosa was based on technologies of IEF, SDS-PAGE, 2DPAGE, by standard sets (MB-HIC C8 Kit, MB-IMAC Cu, MB-Wax Kit, «Bruker», USA). Automated mass spectrometry imaging was performed by matrix-assisted laser desorption-ionization timeof-flight mass spectrometry (MALDI-TOF-MS/MS, Ultraflex II, «Bruker», USA). The partially identified sequences were then submitted to “BLAST protein-protein” and screened against the Homo sapiens Swissprot database to check if this identification matched the MASCOT-identification (Matrix Science, UK). The data of the molecular interactions and functional features of proteins were received with STRING 10.0 database. Based on the data of standard methods of identification of UC and molecular phenotyping of colon mucosa we conducted new prognostic markers, molecular pathways of UC and diagnostic tests in patients with UC. Statistical analysis of the survey data was performed using the software “Statistica 12.0” (Statsoft).

Results

Bioinformatics analysis revealed the presence of molecules that are the participants in the universal pathways of UC in the active stage, and the molecular interactions involved. We identified following functional groups of peptides and proteins in molecular patterns of bioptates of colon mucosa in UC patients: peptides and proteins regulating the barrier function of colon mucosa; proteins-participants of specific metabolism in epitheliocytes and endocrinocytes; proteins of the fibrosis in colon mucosa; proteins regulating cell cycle, oncogenesis, proteolysis in cell, hormones processing, angiogenesis, coagulation factors; proteins of free radical oxidation and antioxidant system; proteins regulating the receptor activity of epitheliocytes and immune cells; structural proteins of colon mucosa; transcription and translation factors regulating the activity of cell nucleus, regulators of protein folding; transport proteins; proteins-enzyms of detoxification. Significant decrease of the PPARγ expression promotes the activation of STAT and AP-1 signaling pathways, which promotes an increase in the synthesis of IL-2,6,8,12, TNFα, matrix metalloproteinases, the activity of immune and inflamation processes in colon mucosa. A significant increase in the NF-kB expression in colon mucosa is associated with the activation of TNFα and IL-1, which promotes the increase of immune processes in colon mucosa. The molecular interactions of β-defensin-1: the reduction of the β-defensin-1 expression in cells of colon mucosa is accompanied by increased expression of CCR6, which promotes the formation of inflammatory infiltrates in colon submucosa in UC.

Conclusion

Identification of potential new molecular markers for UC development may provide opportunities for the development of diagnostic tests to evaluate the disease.

Introduction

Acute Severe ulcerative colitis (ASUC) is a life-threatening medical emergency of colonic inflammatory bowel disease (IBD). Corticosteroids remain the primary initial therapy, although one-third of patients do not respond to treatment. In this perspective, early identification of steroid non-responsive ASUC patients is the key to an effective management and thus, a better prognosis.

Aims & Methods

The aim of our study was to evaluate the impact of CRP/albumin ratio measured on day 3 on treatment outcomes and disease course in ASUC. We conducted a retrospective descriptive study including patients who presented with ASUC over a 10-year period [January 2010 - December 2019]. The diagnosis of ASUC was established on Truelove and Witts criteria and supported by endoscopic findings. Patients demographics were collected; C-reactive protein (CRP) and albumin levels were recorded at baseline and during admission. Data were entered and analyzed by SPSS software version 26.

Results

We included 54 patients with a sex ratio of M/F=0.71. The mean age at diagnosis of IBD was 41.48 years [12-58]. A family history of IBD was noted in 13% of the patients. Twenty-seven patients had Ulcerative Colitis and 27 patients had Crohn´s disease. ASUC was inaugural of the disease in 35% of the patients. For the diagnosis of ASUC, the median number of bloody stools was 7 and the mean CRP level was 91 mg/L. At day 3 of first-line treatment with corticosteroids, the median number of bloody stools was 1 and the mean CRP level was 49 mg/L. First-line treatment failure was noted in 40% (n=20) of the patients with a mean duration of 8 days [3-20]. The mean level of the CRP/albumin ratio on day 3 was 1.8 [0.8-2.9]. Area under the receiver operating characteristic curve analysis showed that this ratio measured on day 3 was highly predictive of steroid non-responsiveness (AUROC=0.69, p=0.02). The optimal cutoff value was 1.6 (sensitivity, 80%; specificity, 57%). There was no significant linear association (Spearman r=-0.11, p=0.64) between this ratio and the timeframe of corticosteroids failure. A significant association was noted between this ratio and the urge to a rescue medical therapy (p=0.015) without being predictive of response (p=0.327). If on day 3, the ratio was higher than 1.6 and bloody stool frequency was beyond 3, the relative risk of steroid non-response was significantly raised at 3.85 (p<0.001) versus 1.7 if only a ratio above 1.6 was considered. As for longer prognosis, this ratio was higher in patients who underwent colectomy within a year of ASUC, without a significant association (n=13, p=0.07), and no correlation was noted with ASUC recurrence (p=0.23).

Conclusion

Our study showed that CRP/albumin ratio on day 3 is not only an effective predictor of non-response to steroids in ASUC, but also predicts the disease course beyond this severe flare-up.