Introduction

Autoantibodies against integrin αvβ6 have recently been associated with ulcerative colitis (UC), its preclinical phase, and UC outcomes. However, data on the diagnostic utility of the autoantibody and its dynamics are scarce. Therefore, we aimed to examine the diagnostic capacity of the anti-αvβ6 autoantibody. Moreover, we assessed its utility in defining a specific phenotype of UC and ascertained its temporal dynamics in relation to the disease course.

Aims & Methods

Using an in-house assay based on the EliA technology (Thermo Fisher Scientific, Uppsala, Sweden), anti-αvβ6 IgG autoantibodies were measured in serum from adult patients with suspected IBD in the Swedish inception cohort SIC IBD (discovery cohort, n=473) and the Norwegian population-based inception cohort IBSEN III (validation cohort, n=570). A cut-off of 400 μg/L was applied, corresponding to the lower calibrator for IgG (4 µg/L) and the 96th percentile of healthy individuals. The course of UC was categorized as indolent or aggressive at 12 months, based on a composite outcome of colectomy, hospital admission for active disease, treatment refractoriness towards ≥2 biological agents, or >2 courses of corticosteroids/cumulative dose of >2.5 g. Inflammatory proteins (n=92) were measured (Olink Proteomics, Uppsala). Welch’s t-test was used with Benjamini-Hochberg correction, applying a 5% false discovery rate (FDR). Linear-mixed models were applied to investigate differences in autoantibody expression between diagnosis and three months follow-up.

Results

The discovery cohort comprised 327 IBD patients and 146 symptomatic controls without any discernible evidence of IBD, and the validation cohort included 366 IBD patients and 204 symptomatic controls. Patients with UC and those with colonic Crohn's disease in the discovery cohort had higher median anti-αvβ6 levels compared to symptomatic controls. The anti-αvβ6 autoantibody demonstrated a sensitivity of 73% and a specificity of 84% for distinguishing UC from CD and symptomatic controls in the discovery cohort and 79% and 91%, respectively, in the validation cohort.
Anti-αvβ6 positivity was associated with a severe UC phenotype, characterized by more extensive colitis (p=0.008), severe Mayo endoscopic activity (p=0.005), and pronounced systemic inflammation, defined as higher hsCRP (p=0.04) and lower albumin concentrations (p=0.01), in the discovery cohort. However, no association of f-Calprotectin was observed. Higher endoscopic activity in anti-αvβ6 positive UC patients was confirmed in the validation cohort. In both cohorts, an increasing extent of inflammation and endoscopic activity was observed with higher median levels of anti-integrin αvβ6.
Five proteins (SYND1, IL-17A, GZMB, MMP1, CXCL13) were significantly upregulated in anti-αvβ6 positive UC patients in the SIC-IBD, and two of them (IL-17A and GZMB) were validated in the IBSEN III cohort. Compared to patients with indolent UC, patients with an aggressive course presented with higher anti-αvβ6 levels at diagnosis in the discovery cohort (p=0.02) and potentially also in the validation cohort (p=0.13). A significant interaction of disease course was observed in autoantibody levels between diagnosis and 3 months in the SIC cohort (p<0.0001), as the levels decreased in patients with indolent UC but not in those with an aggressive course.

Conclusion

Anti-αvβ6 autoantibodies demonstrate a diagnostic capacity for UC and define a severe phenotype of the disease. Its temporal dynamics differ between patients with an aggressive and an indolent disease course.

Disclosure

EP, RM and NR are employed by Thermo Fisher Scientific.

Introduction

Smoking is an environmental and conductual risk factor for the development of Chron’s Disease (CD) and is associated with a more severe course of CD. In contrast, a protective effect is shown in the development and a mild course of Ulcerative Colitis (UC). Smoking leads to cardiovascular disease, cancer and other chronic diseases, and social isolation, anxiety and depression. It is also a predictor of poorer adherence to treatment in young patients.

Results & Findings

50% were women, 52 years old (SD: 12.6). 58.6% suffered CD, 39.7% more than 10 years from onset of disease, 60.7% with biologics; 54.4% in remission and 29.8% mild activity. 24% were active smokers, 60% ex-smokers and 15.5% has never smoked. 60.3% were regular exercisers, and 66% consume alcoholic beverages regularly.
Of those who smoked, 64% were women, 57% suffered CD, 46% was in remission. 85.7% with anxiety and 52.7% with depression, 61.5% perceived their health status as suboptimal. 64.3% consumed alcoholic beverages, 57.1% no physical exercise.
The mean anxiety score was 9 (SD: 3.6), depression score was 5.76 (SD: 3.7). 67.2% had anxiety levels and 32.8% depression. Perceived health status as optimal was 57.9%.
In the bilateral analysis between smoking and the independent variables, only depression and anxiety was associated.

Summary & Discussion

Smoking is an environmental risk factor for the development and course of CD. The aim of this study iis to determine smoking habits and associated factors in patients with Inflammatory Bowel Disease (IBD) in Hospital Universitario del Henares (Madrid).
A transversal study was carried out. Data were collected in a questionnaire ad-hoc and HADS.
Patients with IBD are active smokers, and their percentage is bigger to regular population in Comunidad de Madrid (21.9%). On the other hand, the percentage of ex-smokers with IBD (60%) is much higher than with no IBD; it may be related to IBD development.
It is well known the relationship between IBD and psicosocial aspects. In this study we show the high prevalence of anxiety and depression, which is higher than in general population.
Nurses can play an important role in the psychological care of patients with IBD, especially in prevention and early detection.

Conclusion

Patients with IBD showed a high tobacco consumption, most of which were women and with no healthy habits.
Smoking in patients with IBD is associated with anxiety and depression.

References

(1) Bisgaard TH, Allin KH, Keefer L, Ananthakrishnan AN, Jess T. Depression and anxiety in inflammatory bowel disease: epidemiology, mechanisms and treatment. Nat Rev Gastroenterol Hepatol. 2022;19(11):717-726.
(2) Feng L, Cai X, Zou Q, et al. Exploring the management and treatment of IBD from the perspective of psychological comorbidities. Therap Adv Gastroenterol. 2024;17:17562848241290685.
(3) Barreiro-de Acosta M, Marín-Jiménez I, Panadero A, et al. Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) and the Association of Crohn's Disease and Ulcerative Colitis Patients (ACCU) in the management of psychological problems in Inflammatory Bowel Disease patients. Gastroenterol Hepatol. 2018;41(2):118-127.
(4) Herrero MJ, Blanch J, Peri JM, et al. A validation study of the hospital anxiety and depression scale (HADS) in a Spanish population. Gen Hosp Psychiatry. 2003;25(4):277-83.
(5) Comunidad de Madrid. Dirección de Salud Pública. Resultados del Sistema de Vigilancia Integral del Tabaquismo (VITa). Informe 2023.

Introduction

A reduction of bowel wall thickness (BWT) on intestinal ultrasound (IUS) is an early predictor of endoscopic response in ulcerative colitis (UC).¹ Shear-wave elastography (SWE) may offer additional prognostic information.

Aims & Methods

We aimed to identify early IUS parameters predicting treatment response to filgotinib, a selective JAK-1 inhibitor. This prospective observational study included UC patients with endoscopically active disease starting on filgotinib 200 mg daily. IUS parameters, including SWE, were assessed at baseline (T0), week 4 (T1) and at second endoscopy (T2). The endoscopic Mayo score (EMS) was assessed at T0 and at T2 in both the most-affected segment and the sigmoid. Endoscopic response was defined as a decrease in EMS of at least 1 point.

Results

A total of 23 patients were included. 10 patients were female (10/23, 44%), the mean disease duration was 14.4 years (SD±10.4), and 14 patients (14/23, 61%) had failed 2 or more biologics. Endoscopic response was observed in 6 of the 21 patients (29%) who underwent a second endoscopy after a median of 14 weeks (IQR 12-17). The submucosal thickness in the sigmoid decreased significantly more between T0 and T1 in endoscopic responders compared to non-responders (-40±23.9% vs -11.5±24.5%, p=0.022). At T1, a BWT decrease of ≥1.33 mm or ≥24.7% (OR 32.5 [2.38-443.15], p=0.009 and OR: 13.8 [1.21-156.6], p=0.035) and a submucosal thickness decrease of ≥20.8% (OR: 13.8 [1.21-156.6], p=0.035) predicted endoscopic response at T2. Additionally, improvement in Colour Doppler Signal (CDS) at T1 predicted endoscopic response (OR: 20.0 [1.66-241.7], p=0.018). SWE values in the sigmoid at T0, T1 and T2 were not significantly different between endoscopic responders and non-responders in the sigmoid. While the change in SWE values at T2 compared to baseline was significantly different between the two groups (9.9± 11.5 kPa vs. -8.1 ± 11.4 kPa, p=0.002), the difference at T1 was not significant and did not predict endoscopic response in the sigmoid (OR: 1.07 [0.99-1.16], p=0.088).

Conclusion

On IUS, BWT, submucosal thickness and CDS predict endoscopic response after four weeks of filgotinib treatment. SWE values in the sigmoid changed differently among endoscopic responders and non-responders, but did not predict treatment response.

References

1. de Voogd FA et al. Early Intestinal Ultrasound Predicts Clinical and Endoscopic Treatment Response and Demonstrates Drug-Specific Kinetics in Moderate-to-Severe Ulcerative Colitis. Inflamm Bowel Dis 2023. DOI: 10.1093/ibd/izad274.

Disclosure

MP: none;
CT: none;
FV: received speaker’s fees from AbbVie, Pfizer and Takeda;
RJ: none,
ML: Consultancy/lecture fees from Abbvie, Bristol Myers Squibb, Eli Lilly, Galapagos, Janssen-Cilag, Johnson & Johnson, Medtronic, Pfizer, Takeda, Tillotts. Grants received from Alfasigma, NFU transformation deal, ZonMW and TKI.
RG: received speakers free from Janssen-Cilag BV and Pfizer Inc.
GD: has served as advisor for AbbVie, Abivax, Alimentiv,, Astrazeneca, Bristol Meiers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, , GlaxoSmithKline, Johnson and Johnson, Merck Sharp Dome, Pfizer, Polpharm, Sanofi, Takeda, Tillotts, and received speaker fees from AbbVie, Eli Lilly, Johnson and Johnson, Merck Sharp Dome, , Pfizer, Takeda, Tillotts,.
KG: KB Gecse has received grants from AbbVie, Pfizer Inc, Celltrion and Galapagos; consultancy fees from AbbVie, Arena Pharmaceuticals, ImmunicTherapeutics, Janssen Pharmaceuticals, Novartis, Pfizer Inc., and Takeda and speaker’s honoraria from Abbvie, Celltrion, Eli Lilly, Ferring, Janssen Pharmaceuticals, Pfizer Inc, Takeda and Tillotts.

Introduction

Tumor necrosis factor–like cytokine 1A (TL1A) is a regulator of inflammation and fibrosis in inflammatory bowel disease. Tulisokibart, an anti-TL1A monoclonal antibody, demonstrated efficacy without clinically meaningful safety findings vs placebo after a 12-week induction period in adults with moderately to severely active UC in the phase 2 ARTEMIS-UC study.¹ We report long-term efficacy and safety of tulisokibart among cohort 1 induction responders from the open-label extension (OLE) period of ARTEMIS-UC.

Aims & Methods

ARTEMIS-UC was a phase 2, multicenter, double-blind, placebo-controlled study of tulisokibart in patients with moderately to severely active UC. Cohort 1 enrolled patients regardless of genetic-based diagnostic test (Dx) status whereas cohort 2 enrolled only Dx-positive patients. Patients were randomized to receive intravenous (IV) tulisokibart 1000 mg on day 1 and 500 mg at weeks 2, 6, and 10 or placebo; after the 12-week induction period, all participants had the option to continue in the OLE period. Participants were classified as induction responders (defined as reduction of ≥2 points and ≥30% in modified Mayo score from baseline, accompanied by a reduction ≥1 in rectal bleeding subscore or absolute rectal bleeding subscore ≤1 at week 12) or induction nonresponders. Cohort 1 induction responders in the tulisokibart group were randomized (stratified by Dx status) to receive open-label IV tulisokibart 100 mg or 250 mg every 4 weeks at week 14 until week 170. We report data from cohort 1 through week 50 of the OLE period: clinical and endoscopic efficacy outcomes and biomarkers through week 50 are reported for cohort 1 induction responders from the tulisokibart group whereas safety through week 50 are reported for cohort 1 induction responders from both the tulisokibart group and the placebo group. Descriptive statistics were used to summarize observed data.

Results

47 of 68 tulisokibart-treated patients in cohort 1 were induction responders and were randomized to receive tulisokibart 250 mg (n = 25) or 100 mg (n = 22). Improvements in clinical, endoscopic, and biomarker outcomes observed with tulisokibart were generally maintained through week 50 in both dose groups (Table). However, at week 50, a greater proportion of patients achieved clinical and endoscopic outcomes with tulisokibart 250 mg vs 100 mg. In the safety population, (tulisokibart 250 mg, n = 35; 100 mg, n = 30), through week 50, AEs occurred in 63% and 77% of patients receiving tulisokibart 250 mg and 100 mg, respectively; most were mild to moderate in severity. Serious AEs occurred in 1 patient (3%) and two patients (7%) in the tulisokibart 250 mg and 100 mg groups, respectively.

Conclusion

At week 50, maintenance of treatment effect was generally observed in cohort 1 induction responders in the tulisokibart group. A trend for higher efficacy with tulisokibart 250 mg vs 100 mg maintenance treatment was observed at week 50. Tulisokibart was well tolerated with no identified safety signals. Larger trials are needed to confirm these findings.

References

1. Sands B, et al. J Crohns Colitis. 2023;17(Supplement_1):i56-i59.

Disclosure

CM has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, BioJAMP, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, and Takeda; speaker’s fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Pendopharm, Pfizer, and Takeda; royalties from Springer Publishing; and research support from Ferring and Pfizer.
SH has received advisory fees from Eli Lilly and Tilotts.
MPS has received educational grants or research support from Gilead and Celltrion, speakers fees from Janssen, AbbVie, Ferring, Takeda, Pfizer, Shire, Celltrion, Eli-Lilly and Dr. Falk Pharma, and has served on advisory boards for Janssen, Takeda, Pfizer, Celgene, AbbVie, MSD, Emerge Health, Gilead, BMS, Celltrion, and Eli-Lilly.
JKA, MY, and BD are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA
BGF is a consultant for AbbVie, AbolerIS, AgomAB Therapeutics, Allianthera, Amgen, AnaptysBio, Applied Molecular Transport Inc., Arena Pharma, Atomwise, Avoro Capital Advisors, BioJamp, Biora Therapeutics, Boehringer Ingelheim, Boxer, Bristol Myers Squibb/Celgene, Celsius Therapeutics, Connect BioPharma, Cytoki, Disc Medicine, Duality, EcoR1 Capital, Equillium, Ermium, First Wave, First Word Group, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, GlaxoSmithKline, Gossamer Pharma, Hinge Bio, Hot Spot Therapeutics, Imhotex, Immunic Therapeutics, InDex Pharmaceuticals, JAKAcademy, Janssen, Japan Tobacco Inc., Kaleido Biosciences, Landos Biopharma, Leadiant, L.E.K. Consulting, Lenczner Slaght, LifeSci Capital, Lilly, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic Therapeutics, Mylan, OM Pharma, Origo BioPharma, Orphagen, Pandion Therapeutics, Pendopharm, Pfizer, Play to Know AG, Prometheus Therapeutics and Diagnostics, Progenity, Protagonist, PTM Therapeutics, Q32 Bio, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Surrozen Inc., Takeda, Teva, Thelium, Tigenix, Tillotts, Ventyx Biosciences, VHSquared Ltd., Viatris, Ysios, Ysopia, and Zealand Pharma; on the Speakers’ Bureau for AbbVie, Janssen, and Takeda; and on advisory boards for AbbVie, Amgen, AMT, AnaptysBio, Axio Research, Boehringer Ingelheim, Bristol Myers Squibb/Celgene, EcoR1 Capital, Genentech/Roche, GlaxoSmithKline, InDex Pharmaceuticals, Janssen, Lilly, MiroBio, Morphic, Origo BioPharma, Pfizer, Progenity, Prometheus, REDX Pharma, Sanofi, Takeda, Teva, and Tillotts Pharma.
BES reports consulting fees from AbbVie, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, Astra Zeneca, Biolojic Design, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Envied Biosciences, Evommune, Ferring, Fresenius Kabi, Fiat, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Imhotex, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Kaleido, Kallyope, Merck, Microba, Mobius Care, Morphic Therapeutics, MRM Health, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Therapeutics, Reistone Biopharma, Sanofi, Spyre Therapeutics, Sun Pharma, Surrozen, Target RWE,Teva, TLL Pharmaceutical, Tr1X, Union Therapeutics, Ventyx Biosciences; consulting and speaking fees from Abivax; consulting and speaking fees and other support from Lilly; research grants, consulting and speaking fees and other support from Bristol Myers Squibb, Janssen, Pfizer, Takeda; research grants and consulting fees from Theravance Biopharma; and stock/stock options from Ventyx Biopharma.

Introduction

Accurate diagnosis and monitoring of inflammatory bowel diseases (IBD) are essential for effective management and reduction of complications. Intestinal ultrasound (IUS) is a non-invasive and cost-effective imaging modality for IBD assessment, yet its widespread adoption is limited by operator dependency and interobserver variability. Artificial intelligence (AI) offers the potential to overcome these limitations by improving diagnostic accuracy and standardizing interpretation.

Aims & Methods

This study aimed to develop an AI-assisted model for the automatic detection of active inflammation in IUS images, using bowel wall thickness (BWT) as a key marker. We further aimed to create an automatic tool for detecting bowel segments within ultrasound images and to extend its application from single images to cine loops. Grayscale ultrasound images and cine-loops of the terminal ileum were collected from Crohn’s disease patients undergoing IUS at a tertiary center. The dataset included both normal and abnormal BWT and was annotated by an experienced operator. Preprocessing involved anonymization and normalization. Automated segmentation algorithms were used to isolate bowel wall structures, and deep learning techniques, including convolutional neural networks (CNNs) and YOLO (You Only Look Once) object detection, were employed to analyze the images.

Results

The study included 2,735 grayscale ultrasound images and cine-loops of the terminal ileum from patients with Crohn's disease. The dataset was divided into three sets: a training set of 1980 images, a validation set of 220 images, and a test set of 515 images. Our model achieved robust performance metrics, including sensitivity, specificity, and accuracy of 99.1%, 94.6%, and 91.5%, respectively, for BWT detection, with an area under the receiver operating characteristic curve (AUC) of 0.85. Our model was validated on 10 independent cine-loops, comprising 7 abnormal and 3 normal cases. It accurately identified bowel wall thickening (BWT) in all seven abnormal cases, correctly classifying them as abnormal. Additionally, the model successfully confirmed the absence of BWT in all three normal cine-loops, categorizing them appropriately as normal.

Conclusion

This study represents a significant advancement in the application of artificial intelligence to intestinal ultrasound interpretation by integrating automated segmentation, automatic analysis capabilities, and cine-loop evaluation. Our model extends beyond traditional static image analysis, paving the way for real-time and dynamic assessments of bowel inflammation. This approach highlights the potential of our AI tools to reduce operator dependency, improve diagnostic accuracy, and enhance clinical workflows, making IUS more accessible and reliable for clinicians with varying levels of expertise.

Disclosure

Prof. Dan Carter has received speaker’s fees, research support, or consultancy fees from Takeda, Janssen, AbbVie, and Taro