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OP08: The effects of maintenance therapy with upadacitinib on abdominal pain, bowel urgency, and fatigue in patients with moderately to severely active Ulcerative Colitis: Phase 3 U-ACHIEVE maintenance results
Year: 2022
Source: ECCO'22
Authors: Danese, S.(1);Tran, J.(2);D'Haens, G.(3);Rubin, D.T.(4);Aoyama, N.(5);Zhou, W.(2);James, B.(2);Yao, X.(2);SanchezGonzalez, Y.(2);Panaccione, R.(6);
Created: Friday, 11 February 2022, 3:52 PM
OP09 Immunomodulatory mechanisms of faecal microbiota transplantation are associated with clinical response in ulcerative colitis: early results from STOP-Colitis
Year: 2020
Source:

ECCO'20 Vienna

Authors:

M.N. Quraishi1,2, Y.H. Oo3, A. Beggs4, D. Withers3, A. Acharjee4,5, N. Sharma1,2, S. Manzoor1, A.L. Hart6, D.R. Gaya7, N.J. Loman8, P.M. Hawkey1, K. Gerasimidis9, R. Hansen10, G. Gkoutous4,5,11, T.H. Iqbal1,2

Created: Thursday, 30 January 2020, 10:12 AM
OP09: Histological remission and mucosal healing in a randomised, placebo-controlled, Phase 2 study of etrasimod in patients with moderately to severely active ulcerative colitis
Year: 2019
Source:

ECCO '19 Copenhagen

Authors:

L. Peyrin-Biroulet*1, J. Panés2, M. Chiorean3, J. Zhang4, S. Vermeire5, V. Jairath6, A. Yarur7, C. Cabell4, S. Naik4, W. J. Sandborn8

Created: Friday, 22 February 2019, 9:41 AM
OP09: Immunomodulatory mechanisms of faecal microbiota transplantation is associated with clinical response in Ulcerative Colitis – early results from STOP-Colitis
Year: 2020
Source: ECCO'20 Vienna
Authors: Mohammed Nabil Quraishi
Created: Tuesday, 23 June 2020, 4:58 PM
Files: 1
OP09: Long-term Colectomy rates of Ulcerative Colitis over 40-year of Different Therapeutic eras – Results from a Western Hungarian Population-based Inception Cohort between 1977–2020
Year: 2023
Source: ECCO’23 Copenhagen
Authors: LakatosPhD, P.L.(1)*;Gonczi, L.(2);Lakatos, L.(3);Golovics, P.A.(4);Pandur, T.(5);David, G.(3);Erdelyi, Z.(3);Szita , I.(3);
Created: Friday, 14 July 2023, 10:43 AM
OP09: Oral ritlecitinib and brepocitinib in patients with moderate to severe active Crohn’s Disease: Data from the PIZZICATO umbrella study
Year: 2024
Source: ECCO'24 Stockholm
Authors: Vermeire, Séverine
Created: Tuesday, 30 April 2024, 5:03 PM
OP09: Patient reported outcomes reflect histologic disease activity in patients with Ulcerative Colitis: Interim analysis of the APOLLO study
Year: 2021
Source: ECCO'21 Virtual
Authors: Verstockt, B.(1,2,3);Jorissen, C.(1,2);Hoefkens, E.(1);Lembrechts, N.(1);Pouillon, L.(1);Bossuyt, P.(1,2)
Created: Wednesday, 2 June 2021, 4:12 PM
OP09: Patient reported outcomes reflect histologic disease activity in patients with Ulcerative Colitis: Interim analysis of the APOLLO study
Year: 2021
Source: ECCO'21 Virtual
Authors: Bram Verstockt
Created: Friday, 1 October 2021, 12:41 PM
Background

Treating beyond endoscopic remission, aiming for histological remission, has shown to reduce relapse and hospitalization rates in patients with ulcerative colitis (UC). However, very little is known on how histological remission associates with patient reported outcomes (PROMs).

Methods

PROMs (Simple clinical colitis activity index [SCCAI], IBD disk and Visual Analogue Scales [VAS]) were prospectively collected through a digital questionnaire in all patients with UC undergoing colonoscopy between July 21st 2020-Jan 21st 2021. Mayo endoscopic sub score and UCEIS were determined, as well as the Nancy histologic index (NHI) of the most affected area. Endoscopic remission was defined as Mayo endoscopic sub score 0 and UCEIS 0; histologic remission as NHI 0, absence of active inflammation as NHI ≤ 1. PRO2 remission was defined as stool frequency ≤ 1 (absolute stool frequency ≤ 3 OR 1-2 stools more than usual) and rectal bleeding score of 0.

Results

Fifty-six paired assessments were collected in 48 unique patients (Table 1), with a histologic, endoscopic and PRO-2 remission rate of 23.2%, 28.6% and 38.2% respectively. Patients with histologic remission or absence of histologic inflammation had a significantly lower overall IBD disability (p=0.007, p=0.003) and disease activity score (p=0.003, p<0.001), as compared to patients without. In line, NHI correlated with the overall IBD disk (r=0.40, p=0.002) and SCCAI score (r=0.50, p<0.001). Many individual components of both scores (abdominal pain, arthralgia, impact on education and work/interpersonal interactions/sexual function, regulation of defecation, blood loss, general wellbeing, joint pain, numbers of stools during night/day, urgency) differed significantly between patients with and without histologic remission. VAS scores assessing general wellbeing (r=0.33, p=0.01), impact on daily activities (r=0.41, p=0.002), UC-related symptoms (r=0.42, p=0.001) and worries (r=0.40, p=0.002) correlated with histology.  Quartile analysis of the overall IBD disk and SCCAI scores confirmed the highest likelihood for histologic remission in patients with the lowest scores (Q1-Q2 vs Q3-Q4 39.3% vs 7.1%, p=0.01; 40.0% vs 9.7%, p=0.01) (Figure 1). Nevertheless, the overall accuracy of the IBD disk (0.75) or SCCAI score (0.76) for histologic remission is lower (p<0.05) than the accuracy of the Mayo endoscopic (0.90) or UCEIS (0.90) score.

Table 1 : Baseline features

Figure 1 : Quartile analysis
Conclusion

In patients with UC, PROMs for disability and clinical disease activity reflect histologic disease activity and should therefore be further explored in (trial) endpoint discussions. However, they cannot fully replace endoscopic and histologic findings, and should be considered complementary.

OP09: Proactive Therapeutic Drug Monitoring is superior to standard treatment during maintenance therapy with infliximab; results from a 52-week multicentre randomised trial of 450 patients; the NOR-DRUM B study
Year: 2022
Source: ECCO'22
Authors: Jørgensen, K.K.(1);Syversen, S.W.(2);Goll, G.L.(2); Bjørlykke, K.H.(1,3);Sandanger, Ø.(4);Sexton, J.(2);Brun, M.K.(2,3);Noraberg, G.(5);Ystrøm, C.M.(6); Seeberg, K.A.(7);Blomgren, I.M.(8);Torp, R.(9);Mørk, C.(10);Kvien, T.K.(2,3); Bolstad , N.(4);Haavardsholm, E.A.(2,3);Jahnsen, J.(1,3); The NOR-DRUM study group
Created: Friday, 11 February 2022, 3:52 PM
OP10 IgA coating of intestinal microbiota is associated with inflammatory bowel disease in twin pairs discordant for inflammatory bowel disease
Year: 2020
Source:

ECCO'20 Vienna

Authors:

E. Brand1, Y. Laenen2, F. van Wijk3, M. de Zoete4, B. Oldenburg5, On behalf of the Dutch TWIN-IBD Consortium

Created: Thursday, 30 January 2020, 10:12 AM
OP10: Comparative efficacy of biologics for endoscopic healing of the ileum and colon in Crohn’s Disease
Year: 2022
Source: ECCO'22
Authors: Narula, N.(1);Wong, E.(1);Dulai, P.(2);Marshall, J.(1);Jairath, V.(3);Reinisch, W.(4);
Created: Friday, 11 February 2022, 3:52 PM
OP10: IgA coating of intestinal microbiota is associated with Inflammatory Bowel Disease in twin pairs discordant for Inflammatory Bowel Disease
Year: 2020
Source: ECCO'20 Vienna
Authors: Eelco Brand
Created: Tuesday, 23 June 2020, 4:58 PM
Files: 1
OP10: Proctocolectomy with permanent ileostomy is associated with better transplant-free survival in patients with primary sclerosing cholangitis: a retrospective cohort study
Year: 2023
Source: ECCO’23 Copenhagen
Authors: Mol, B.(1)*;van Nieuwamerongen, M.(1);van Munster, K.(1);van Munster, S.(1);de Vries, A.(2);van der Meer, A.(2);Goet, J.(2);Weersma, R.(3);Inderson, A.(4);Boonstra, K.(1);van Meer, S.(5);de Boer, Y.(1);Spanier, M.(6);Drenth, J.(7);de Vries, E.(8);Beuers, U.(1);Bogaards, J.(9);Ponsioen, C.(1);
Created: Friday, 14 July 2023, 10:43 AM
OP10: Response to biologics in IBD patients assessed by Computerized image analysis of Probe Based Confocal Laser Endomicroscopy with molecular labeling and gene expression profiling
Year: 2021
Source: ECCO'21 Virtual
Authors: Iacucci, M.(1,2,3);Jeffery, L.(1);Acharjee, A.(4);Nardone, O.M.(1);Smith, S.C.(1);Labarile, N.(1);Zardo, D.(5);Cannatelli, R.(1);Shivaji, U.N.(1);Ungar, B.(1);Buda, A.(6);Grisan, E.(7);Gkoutos, G.(4);Subrata, G.(1,2,3)
Created: Wednesday, 2 June 2021, 4:12 PM
OP10: Response to biologics in IBD patients assessed by Computerized image analysis of Probe Based Confocal Laser Endomicroscopy with molecular labeling and gene expression profiling
Year: 2021
Source: ECCO'21 Virtual
Authors: Marietta Iacucci
Created: Friday, 1 October 2021, 12:41 PM
Background

Biologics are being used increasingly in the treatment of Inflammatory Bowel Disease. However, up to 40% of patients do not respond to biologics. Therefore, methods to predict response are imperative. We aimed to identify novel genes and pathways predictive of anti-TNF response in patients with Ulcerative Colitis (UC) undergoing electronic chromoendoscopy and probe confocal laser endomicroscopy (pCLE). We further evaluated the ex-vivo binding of fluorescent labelled biologics as markers of response

Methods

26 UC patients starting anti-TNF therapy as standard of care were recruited. Pre-treatment colonoscopy, with electronic chromoendoscopy and pCLE (Cellvizio, Mauna Kea) by injecting intravenous fluorescein (2.5-5mls), was performed to assess disease activity. Targeted biopsies were taken for fluorescein isothiocyanate (FITC)-labelled infliximab staining and RNA extraction and gene expression analysis. Ex vivo labelling was evaluated by an automated analysis: after a first pre-processing step to remove biases, the labelled regions were identified using statistical multi-level thresholding, and evaluated as area and intensity. To assess response, the same endoscopic procedure was repeated at week 12-14 after anti-TNF. cDNA libraries were prepared using QIAseq UPX 3’Transcriptome reagents and sequenced. Normalised gene expressions were obtained through the CLC Genomics Workbench. Differentially expressed genes (DEGs) (FDR-corrected P-value<0.05) were determined using the Limma package and PLS-DA modelling performed to calculate their importance (VIP score). Functionally related genes were identified and classified using DAVID tools. Strongest indicators of response were predicted by Random Forest area under the curve (AUC) analysis in this cohort and a similar validation cohort

Results

At baseline increased binding of the labelled biologic was associated with a higher likelihood of response to treatment  (AUROC81%, accuracy77%, PPV100%, NPV63%). 342 DEGs (75 up-regulated, 267 down-regulated) distinguished responders from non-responders, 76 fell within enriched pathways. Pathways related to inflammation, chemotaxis, TGF-beta signalling, extracellular matrix and carbohydrate metabolism were reduced and cell-cell adhesion increased in responders pre-treatment. Among the 37 genes with VIP>1, CRIP2, CXCL6,EMILIN1,GADD45B, LAMA4 and MAPKAPK2 were upregulated in non-responders pre-treatment and were good predictors of response (AUROC>0.7) in this cohort and validation cohort








Conclusion

A higher mucosal binding of the biologics before treatment was observed in anti-TNF responders. Responsive UC patients have a less inflamed and fibrotic state pre-treatment. Chemotactic pathways, involving CXCL6 may be novel targets to treat non-responders