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Introduction

To compare the efficacy of therapy mesenchymal stromal cells (MSCs), bone marrow, and the standard anti-inflammatory therapy in the extra-intestinal manifestations (sacroiliitis and ankylosing spondylitis) in patients with Crohn's disease (CD).

Aims & Methods

34 CD patients with extraintestinal manifestations (ankylosing spondylitis and sacroiliitis, are not related to the activity of Crohn's disease) were divided into two groups. The first group of patients aged 18 to 58 years (Me-34) (n=16) received MSCs culture scheme (0-1-2-3, then every 26 weeks). The second group of patients with CD (n=18) aged 20 to 60 years old (Me-28) received standard anti-inflammatory therapy with glucocorticosteroids (GCS) and immunosuppressive (IS). Evaluation of efficacy was conducted on the level of activity of inflammation (CRP, thrombocytosis) and ankylosing spondylitis activity index (BASDAI) were performed at 12, 25 and 52 weeks of therapy.

Results

Among the patients in Group 1 reduction in the activity of the AS after 12 weeks of observation occurred in 4/16 patients (25.9%). In group 2, a decrease in activity of the AS occurred in 5/18 (27.7%) (p=0.83).
After 26 weeks in patients (group 1) receiving MSCs, reducing the activity of the AS occurred in 10/16 (62.5%). In group 2, a decrease in activity of the AS occurred in 5/18 (27.7%) (p=0.044).
After 52 weeks in group 1 patients the minimal activity of the AS persisted in 10/16 (62.5%) patients with CD. In group 2, there was increased activity of the AS in one patient 4/18 (22.2%) (p=0.042).

Conclusion

MSCs transplantation can reduce the activity of the AS associated with Crohn's disease compared to standard anti-inflammatory GCS/IS therapy.

TREATMENT OF BONE MARROW MESENCHYMAL STROMAL CELLS REDUCES THE ACTIVITY ANKYLOSING SPONDYLITIS ASSOCIATED WITH CROHN'S DISEASE

Oleg Knyazev 1, Anna Kagramanova 2

1 Moscow Clinical Scientific Center named after A.S. Loginov, Moscow, Russian Federation|||State Scientific Centre of Coloproctology named after A.N. Ryzhyh, Moscow, Russian Federation

2 Moscow Clinical Scientific Center named after A.S. Loginov, Moscow, Russian Federation

Conference

UEG Week Copenhagen 2023

Topics

IBD

Submission format

Abstract

Session

PP 05 IBD (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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Introduction

Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract with recurrent nature of the flow. The frequency of exacerbations is approximately 20-25% at 1 year and 75% for 3 years. If the remission lasted less than 12 months, there is a 65% chance that the aggravation comes in the next 18 months. For the duration of remission for 12 months or more the likelihood of an explosion in the next 18 months is reduced to 20%.

Aims & Methods

To evaluate the influence of culture of allogeneic mesenchymal stromal cells (MSCs) of bone marrow for the duration of remission in patients with refractory CD.
Materials and Methods. The first group of patients with CD (n=30) received MSCs, the dose of prednisone was not more than 20 mg/day. The second group of patients (n=30) received standard anti-inflammatory drug therapy of 5-aminosalicylic acid (5-ASA) and glucocorticosteroids (GCS). Age of patients ranged from 19 to 49 years (Me-36 years). The disease was of moderate and high activity, length of damage - ileokolit, ileitis and colitis, the observation time ranged from 68 to 118 months. Clinical activity was assessed by the Crohn's disease activity index (CDAI). The culture of allogeneic MSCs injected drip at 2.5 million per 1 kg of body weight (0-1-26-52 weeks and twice a year).

Results

CDAI in the 1-st group was 242,6±11,7 points, in the 2-nd 240,9±12,9 points (p=0,83), CRP levels in 1-st group was 29,3±6.4 mg/l, the 2-nd - 27,8±4,8 (p=0,47). After 1 year of follow-CDAI in 1-st group was 70,0±11,0 points, in the 2-nd - 133,8±22,2 points (p<0,001), CRP levels in 1-st group was 6,36±1,5 mg/l, in the 2-nd - 12,2±2,9 (p<0,001). After 5 years - the CDAI in 1-st group - 120,0±22,3 points, in the 2-nd - 208,7±17,6 points (p<0,001), CRP levels in 1-st group - 11,3±2,6 mg/l, in the 2-nd - 15,5±2,4 (p<0,001). After 10 years - the CDAI in 1-st group - 126,0±23,8 points, in the 2-nd - 248,7±14,6 points (p<0,001), CRP levels in 1-st group was 12, 3±2,8 mg/l, in the 2-nd - 19,5±3,1 (p <0,001). In the first group of patients in remission after 1, 5 and 10 years was kept at 70%, 46.7% and 43.3%, respectively. In the second group of patients at 1, 5 and 10 year remission was maintained at 36.6%, 6.67% and 6.67%, respectively.

Conclusion

Transplantation of MSCs contributes to longer-term clinical and endoscopic remission in patients with refractory Crohn's disease compared with therapy with corticosteroids.

THE EFFECTIVENESS AND SAFENESS OF ALLOGENEIC MESENCHYMAL STROMAL CELLS OF BONE MARROW IN PATIENTS WITH REFRACTORY CROHN'S DISEASE - 10 YEARS OF OBSERVATION

Oleg Knyazev 1, Anna Kagramanova 2, Albina Lishchinskaya 2, Asfold Parfenov 2

1 Moscow Clinical Scientific Center named after A.S. Loginov, Moscow, Russian Federation|||State Scientific Centre of Coloproctology named after A.N. Ryzhyh, Moscow, Russian Federation

2 Moscow Clinical Scientific Center named after A.S. Loginov, Moscow, Russian Federation

Conference

UEG Week Copenhagen 2023

Topics

IBD

Submission format

Abstract

Session

PP 05 IBD (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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Introduction

Crohn’s disease (CD) complicated with intra-abdominal abscess often requires surgical intervention. Image guided percutaneous drainage (PD) can help to avoid surgical interventions, however there is limited evidence on the optimal management after PD.

Aims & Methods

Our study aimed to analyze the long-term outcomes of CD complicated with intra-abdominal abscess after intervention. In this multicenter, interational retrospective trial penetrating CD patients with simplex intra-abdominal abscess were enrolled and followed until 12-24 months. Baseline was the day of the first detection of abdominal abscess. Patients with urgent resection were excluded. Patients were grouped based on elective surgical need during follow-up after a successful PD, while the control group consisted of patients who underwent resection without PD. Primary outcome was the abscess recurrence, while stoma rate, post procedural complications rate (<30 days), need for re-drainage and postoperative luminal recurrence were analyzed as secondary outcomes.

Results

A total of 151 CD patients from 9 countries were recruited and 86/151 patients had PD due to simplex abdominal abscess (Table 1.). Abscess recurrence rates were similar (12.8% vs. 7.7%, p=0.231). Need for re-drainage was more common amongst PD patients (OR=0.088, 95% CI=0.011-0.682), while hospital admission need was more frequent in control patients (OR=2.56, 95% CI=1.22-5.37). Postoperative luminal recurrence, new stoma, and biological treatment escalation needs were similar between groups based on PD. Surgical complications were coupled with increased odds in patients without prior PD (OR=3.3, 95% CI=1.09-10.0), septic complications, perforation and new fistula formation were reported the most, while PD associated complication did not occur. Higher baseline diameter of the abscess increased the odds for postoperative recurrence (OR=1.05, 95% CI=1.02-1.08) and new biological treatment initiation (OR=0.98, 95% CI=0.96-0.98). Elective resection was delayed after PD compared to control (24 vs 10 week, p=0.003). Time until resection increased the odds for redrainage (OR=1.03, 95% CI 1.01-1.05), and outcome was worse exceeding 17 weeks.

Variables	Total (n = 151)	PD group (n = 86)	Control group (n = 65)	Sig.
FU duration, weeks, median (IQR)	103 (71-109)	104 (64-112)	101 (77-105)	0.895
Sex, male (%)	88 (58.3)	49 (57.0)	39 (60.0)	0.419
Age at inclusion, years, median (IQR)	33.0 (26-44)	36.3 (27-46)	30.2 (25-38)	0.006
CD disease duration at inclusion, years, median (IQR)	11 (6-17)	11 (5-18)	11 (7-17)	0.916
Disease activity at baseline
CDAI, mean (± SD)	302 (109)	290 (126)	307 (115)	0.389
CRP, mg/l, mean (±SD)	92 (57)	112 (88)	107 (80)	0.753
SES-CD, mean (±SD)	10.0 (8.1)	7.1 (5.8)	12.0 (9.0)	0.071
Elective resection during FU, n (%)	126 (83.4)	61 (70.9)	65 (100)	-

Conclusion

The size of the abscess determines the outcomes, while surgical treatment alone may be associated with post-procedural complications. PD may delay resection; however, this delay can necessitate re-drainage.

ANALYSIS OF INVASIVE TREATMENT STRATEGIES FOR SIMPLEX ABDOMINAL ABSCESS IN CROHN’S DISEASE: A RETROSPECTIVE, MULTICENTRE COHORT STUDY

Péter Bacsur 1, Sylwia Nemeczek 2, Rafal Filip 2, Fotios Fousekis 3, Konstantinos Mpakogiannis 3, Ploutarchos Pastras 4, Andreas Blesl 5, Sophie Vieujean 6, Yvette Gatt 7, Marko Brinar 8, Anna Kagramanova 9, Ákos Iliás 10, Lorant Gonczi 10, Pal Miheller 10, Tamás Resál 11, János Tajti 12, Emese Ivány 13, Bernadett Farkas 13, Anita Balint 13, Anna Fabian 13, Renáta Bor 13, Mariann Rutka 13, Zsofia Bosze 13, Dániel Magyar 13, Zoltán Szepes 13, Klaudia Farkas 13, Tamás Molnár 13

1 University of Szeged, Albert Szent-Györgyi Medical School, Szeged, Hungary|||HCEMM-USZ, Szeged, Hungary

2 Clinical Hospital No. 2, Rzeszow, Poland|||Medical College of Rzeszow University, Rzeszow, Poland

3 Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece

4 University Hospital of Patras, Patras, Greece

5 Medical University of Graz, Graz, Austria

6 University Hospital CHU of Liège, Liège, Belgium

7 Mater Dei Hospital, Msida, Malta

8 University Hospital Centre Rebro, Medical School, University of Zagreb, Zagreb, Croatia

9 The Loginov Moscow Clinical Scientific Centre, Moscow, Balaschiha, Russian Federation

10 Semmelweis University, Budapest, Hungary

11 HCEMM-USZ, Szeged, Hungary|||Central Hospital of Northern Pest - Military Hospital, Budapest, Hungary

12 Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary

13 University of Szeged, Albert Szent-Györgyi Medical School, Szeged, Hungary

Conference

UEG Week Berlin 2025

Topics

IBD

Submission format

Abstract

Session

IBD (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Introduction

Type 2 Glycoprotein (GP2) is a quantitatively predominant membrane protein of excretory granules of pancreatic acinar cells. In a number of studies, it has been demonstrated that this protein is the main antigen for pancreatic antibodies associated with Crohn's disease Zonulin – a protein that can reversibly increase the permeability of the intestinal wall by changing the structure of tight junctions of the lateral surfaces of intestinal epithelial cells. The determination of fecal zonulin is used for noninvasive assessment of increased intestinal permeability. Normal values of fecal zonulin (≤ 110 ng/ml) indicate the absence of damage to the villous surface of the intestinal mucosa and normal density of intercellular contacts

Aims & Methods

The aim of the study was to establish the dependence of the level of type 2 glycoprotein on the level of fecal zonulin (FZ) in the feces of CD patients with exacerbation of the disease.
Material and methods. 217 patients with CD in remission of the disease (Ме age — 38 years) were examined. FZ was evaluated by ELISA (IDK ® Zonulin ELISA Kit, Immunodiagnostik AG, Germany) in ng/ml. Reference values: < 83.15 ng/ml - a variant of the norm, 83.15-110 ng/ml - an elevated level, 110 ng/ml - a high level.
The level of IgG and IgA to GP2 (antibodies to glycoprotein) antigen of pancreatic centroacinar cells (Anti-GP2, IgG, IgA) was determined by ELISA. Reference values: IgG GP-2 less than 10 units/ml, Ig And GP-2 less than 5 units/ml – positive values.

Results

In the stool samples of CD patients during remission in 76 (35%) patients, an increase in the FZ was detected, the average value was 235.4±11.6 ng/ml. In the blood samples of 59 (27.2%) CD patients during remission, an increase in Ig A GP-2 was detected, the average value was 24.4±1.9 units/ml. In the blood samples of 137 CD patients during remission, an increase in Ig G GP-2 was detected, the average value was 19.7±1.1 units/ml. There is no correlation between the concentration of FZ and the concentration of Ig A GP-2 (r-0.260) (p>0.05). There is a moderate correlation force (r-0.310) (p=0.033) between the concentration of FZ and the concentration of Ig G GP-2.

Conclusion

There is no correlation between the concentration of FZ in the feces of CD patients during remission with the concentration of Ig A GP-2 and Ig G GP-2 in the blood serum of patients.

THE DEPENDENCE OF THE CONCENTRATION OF TYPE 2 GLYCOPROTEIN ON THE CONCENTRATION OF ZONULIN IN CROHN'S DISEASE DURING REMISSION OF THE DISEASE

Anna Kagramanova 1, Oleg Knyazev 2, Alexandr Novikov 1, Elena Alexandrova 1, Bella Nanaeva 3, Raisa Gudkova 1, Dmitriy Kulakov 1, Asfold Parfenov 1

1 Moscow Clinical Scientific Center named after A.S. Loginov, Moscow, Russian Federation

2 Moscow Clinical Scientific Center named after A.S. Loginov, Moscow, Russian Federation|||State Scientific Centre of Coloproctology named after A.N. Ryzhyh, Moscow, Russian Federation

3 State Scientific Centre of Coloproctology named after A.N. Ryzhyh, Moscow, Russian Federation

Conference

UEG Week Copenhagen 2023

Topics

IBD

Submission format

Abstract

Session

PP 05 IBD (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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Introduction

Type 2 glycoprotein (GP2) is a quantitatively predominant membrane protein of excretory granules of pancreatic acinar cells. In a number of studies, it has been demonstrated that this protein is the main antigen for pancreatic antibodies associated with Crohn's disease (CD). Zonulin – a protein that can reversibly increase the permeability of the intestinal wall by changing the structure of tight junctions of the lateral surfaces of intestinal epithelial cells. The determination of fecal zonulin is used for noninvasive assessment of increased intestinal permeability. Normal values of fecal zonulin (≤ 110 ng/ml) indicate the absence of damage to the villous surface of the intestinal mucosa and normal density of intercellular contacts.

Aims & Methods

The aim of the study was to establish the dependence of the level of type 2 glycoprotein on the level of fecal zonulin (FZ) in the feces of CD patients with exacerbation of the disease.
Material and methods. 122 patients with CD in the form of ilekolitis with exacerbation of the disease (Me age — 32 years) were examined. FZ was evaluated by ELISA (IDK ® Zonulin ELISA Kit, Immunodiagnostik AG, Germany) in ng/ml. Reference values: < 83.15 ng/ml is a variant of the norm, 83.15-110 ng/ml is an elevated level, 110 ng/ml is a high level.
The level of IgG and IgA to GP2 (antibodies to glycoprotein) antigen of pancreatic centroacinar cells (Anti-GP2, IgG, IgA) was determined by ELISA. Reference values: IgG GP-2 less than 10 units/ml, Ig and GP-2 less than 5 units/ml – positive values.

Results

In the stool samples of CD patients during the period of exacerbation in 92 (75,4%) patients, an increase in FZ was detected, the average value was 333.4 ±16.9 ng/ml. In the blood samples of 81 (66,4%) patients with CD during the period of exacerbation, an increase in Ig A GP-2 was detected, the average value was 43.4±6.9 units/ml. In the blood samples of 107 CD patients during the period of exacerbation, an increase in Ig G GP-2 was detected, the average value was 17.1 ± 1.3 units/ml. There is a high correlation force between the concentration of FZ and the concentration of Ig A GP-2 (r-0.760) (p=0.010). There is a moderate correlation force (r-0.490) (p=0.023) between the concentration of FZ and the concentration of Ig G GP-2.

Conclusion

An increase in the concentration of FZ in the feces of CD patients during exacerbation significantly correlates with an increase in the concentration of Ig A GP-2 and Ig G GP-2.

THE DEPENDENCE OF THE LEVEL OF GLYCOPROTEIN TYPE 2 ON THE LEVEL OF ZONULIN IN CROHN'S DISEASE

Anna Kagramanova 1, Oleg Knyazev 2, Albina Lishchinskaya 1, Raisa Gudkova 1, Karina Noskova 1, Elena Alexandrova 1, Alexandr Novikov 1, Alexandra Demchenko 1, Bella Nanaeva 3, Asfold Parfenov 1

1 Moscow Clinical Scientific Center named after A.S. Loginov, Moscow, Russian Federation

2 Moscow Clinical Scientific Center named after A.S. Loginov, Moscow, Russian Federation|||State Scientific Centre of Coloproctology named after A.N. Ryzhyh, Moscow, Russian Federation

3 State Scientific Centre of Coloproctology named after A.N. Ryzhyh, Moscow, Russian Federation

Conference

UEG Week Copenhagen 2023

Topics

IBD

Submission format

Abstract

Session

PP 05 IBD (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

UEG Standards and Guidelines

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Abstract

This article is the second in a series of two publications on the European Crohn’s and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn’s disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn’s disease and an update of prior ECCO Guidelines.

ECCO Guidelines on Therapeutics in Crohn's Disease: Surgical Treatment

Michel Adamina

Publisher

European Crohn’s and Colitis Organisation

Guideline

Clinical Practice Guideline

Topics

IBD Surgery

Citation

Journal of Crohn's and Colitis, Volume 18, Issue 10, October 2024, Pages 1556–1582

Published

2024

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Introduction

Approximately 10-15% of patients with Crohn's Disease (CD) experience penetrating complications during disease course, which significantly burdens patients' lives and impacts the healthcare system. Efficacy and safety of adipose-derived mesenchymal stem cell (MSC) transplantation (darvastrocel) in treating CD complicated by complex perianal fistulas are contradicting and real-world data are lacking.

Aims & Methods

Our study aimed to assess the effectiveness and safety of MSC therapy in managing perianal Crohn’s disease. This was a retrospective, multicenter cohort study enrolling CD patients with perianal fistulas. Baseline is defined as the day of MSC treatment while the follow-up is set at 6 to 12 months. Primary outcome was perianal clinical remission at w26 (defined by closure of all external openings), while secondary outcomes were clinical response rate, perianal clinical activity (defined by Perianal Disease Activity Index [PDAI]), and adverse events. Demographic, clinical, and surgical data were recorded at baseline, w12, w26, and at w52. Predictors of treatment failure were analyzed by logistic regression models.

Results

Overall, data of 69 patients (male/female ratio was 0.52 and median age was 36 [IQR 31-44]) were analyzed with a median follow-up duration of 52 [IQR 48-53] weeks. Perianal clinical remission was achieved in 49.3% until w26 and 44.9% (intention-to-treat) and 53.44% (per protocol) until w52, while baseline PDAI (OR 0.77, p = 0.043) score was associated with treatment failure. Characteristics of perianal fistulas were not linked to primary outcome. Clinical response rates were 69.6% at w26 and 78.3% (intention-to-treat) and 74.1% (per protocol) at w52. PDAI scores were decreased to w52 (5.2 [±3.1] to 3.2 [±2.8], p < 0.001). Worsening of perianal symptoms were not recorded, while improvement was reported in 78.8%, 81.1%, and 85.7% of cases at w12, w26, and w52. Total adverse events occurred in 8.7%, which were needed surgical reintervention. Furthermore, emerging stenosis, anal incontinence and severe infection were not registered.

Table 1. Baseline demographic and clinical characteristics of enrolled patients

Variables	CD (n = 69)
Follow-up duration, weeks, median (IQR)	52 (48 - 53)
Sex, male (%)	36 (52.2)
Age at inclusion, years, median (IQR)	36 (31 - 44)
Disease duration at inclusion, weeks, median (IQR)	11 (7 - 18)
Disease activity
CDAI, mean (± SD)	61,2 (53)
PDAI, mean (± SD)	6,9 (3,4)
CRP, mg/l, mean (± SD)	3,8 (5,2)
Number of fistulas, mean (± SD)	2 (1)

Conclusion

Efficacy data are consisted with the registration ADMIRE study, more than 80% of patients benefit from the treatment, however the appearance of spontaneous closure is high in the literature. The safety profile is reassuring, and patients’ satisfaction is high.

EVALUATION OF THE EFFECTIVENESS AND SAFETY OF MESENCHYMAL STEM CELL TREATMENT IN FISTULIZING CROHN’S DISEASE – INTERNATIONAL, MULTICENTER, RETROSPECTIVE COHORT STUDY

Péter Bacsur 1, Daniel Shaham 2, Tamás Resál 3, Bernadett Farkas 4, Patrícia Sarlós 5, Pal Miheller 6, Nitsan Maharshak 2, Meir Zemel 2, Ariella Shitrit 7, Anita Balint 4, Anna Fabian 4, Renáta Bor 4, Zsofia Bosze 4, Emese Ivány 4, Szepes Zoltán 4, Klaudia Farkas 1, Zuzana Serclova 8, Szabolcs Ábrahám 4, Tamás Molnár 4

1 University of Szeged, Szeged, Hungary|||HCEMM-USZ Translational Colorectal Research Group, Szeged, Hungary

2 Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

3 Military Hospital-State Health Center, Budapest, Hungary|||University of Szeged, Szeged, Hungary

4 University of Szeged, Szeged, Hungary

5 University of Pécs, Pécs, Hungary

6 Semmelweis University, Budapest, Hungary

7 Shaare Zedek Medical Center, Jerusalem, Israel

8 Surgical Department, NH Hospital, Horovice, Czechia

Conference

UEG Week Vienna 2024

Topics

IBD

Submission format

Abstract

Session

IBD (Posters)

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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