Vedolizumab has chemopreventive properties with regard to colorectal neoplasia (CRN) in the high-risk group of patients with PSC-IBD.
ID
Bron
Verkorte titel
Aandoening
Primair scleroserende cholangitis, primary sclerosing cholangitis, Inflammatory bowel disease, inflammatoire darmziekte, Ulcerative Colitis, Colitis Ulcerosa.
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
Differences in expression of previously identified potential biomarkers with regard to copy number changes, cancer-relevant gene mutations, methylation status, as well as MIF expression in patients with PSC/IBD versus IBD, stratified by vedolizumab treatment.
Achtergrond van het onderzoek
Primary sclerosing cholangitis (PSC) is a rare chronic inflammatory disease of the biliary tree of unknown cause. Therapy is still limited to treatment of complications, and ultimately leading to bile duct destruction and liver failure. PSC has a strong association with inflammatory bowel disease (IBD), especially ulcerative colitis (UC). The gut homing lymphocyte paradigm offers a plausible explanation linking the gut and liver in PSC, stating that gut-primed t-lymphocytes (expressing á4â7) can migrate into the liver because of aberrantly expressed adhesion molecules (like MAdCAM-1) and chemokines in the liver. Vedolizumab is a humanized monoclonal antibody, that specifically binds to the lymphocyte integrin á4â7, thereby impairing the migration of gut-homing lymphocytes into gastrointestinal mucosa and possibly into the liver.
The risk of developing colorectal carcinoma (CRC) is elevated in patients with PSC and concomitant IBD compared to patients with IBD alone, with an estimated cumulative risk of 13% after 30 years. This mandates annual colonoscopic surveillance from the date of diagnosis of PSC, which is a burden for the patients. A clinically useful biomarker assay for early detection of the dysplasia-carcinogenesis sequence could help in surveilling these patients. Previous research showed an increased expression of Macrophage Migration Inhibitory Factor (MIF) in right colonic mucosal tissue of PSC/IBD patients as opposed to IBD-patients. In gastrointestinal cancers, an increase of this inflammatory cytokine is seen. Blocking T-cell influx into the colonic tissue could possibly decrease MIF levels in the colonic mucosa, vedolizumab may play a role in this process.
With this study, we aim to test the hypothesis that vedolizumab has chemopreventive properties with regard to colorectal neoplasia in the high-risk group of patients with PSC/IBD and look into the feasibility of potential biomarkers of risk of development of CRC in PSC/IBD patients.
Doel van het onderzoek
Vedolizumab has chemopreventive properties with regard to colorectal neoplasia (CRN) in the high-risk group of patients with PSC-IBD.
Onderzoeksopzet
Group 1: 3 colonoscopies with 1 year in between
Group 2: 2 colonoscopies with approximately 2 years in between
Onderzoeksproduct en/of interventie
During surveillance endoscopy (scheduled in regular care):
- 8 colonic biopsies
- SES-CD or UCEIS/Mayo score
- 2 blood samples
- 1 fecal sample
In case of PSC-IBD: 3 subsequent surveillance colonoscopies, in case of only IBD: 2 subsequent surveillance colonoscopies.
Algemeen / deelnemers
Academic Medical Center<br>
P.O. Box 22700
Cyriel Y. Ponsioen
Amsterdam 1100 DD
The Netherlands
c.y.ponsioen@amc.nl
Wetenschappers
Academic Medical Center<br>
P.O. Box 22700
Cyriel Y. Ponsioen
Amsterdam 1100 DD
The Netherlands
c.y.ponsioen@amc.nl
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
Group 1:
- Diagnosis of PSC, established by cholangiography, in whom secondary causes of sclerosing cholangitis have been excluded
- Concurrent diagnosis of IBD (either UC, CD or IBDU), established at least 3 months prior to enrollment by clinical and endoscopic evidence and corroborated by a histopathology report
- Age 18 years and older, either male or female
- Ability to give informed consent
- Groups will be stratified for the use of thiopurines
- Groups will be stratified for UC, CD and IBDU
Group 2:
- Diagnosis of IBD (either UC, CD or IBDU), established at least 3 months prior to enrollment by clinical and endoscopic evidence and corroborated by a histopathology report
- Age 18 years and older, either male or female
- Ability to give informed consent
- 10 patients with routine vedolizumab treatment, 10 patients without vedolizumab treatment
- Groups will be stratified for the use of thiopurines
- Groups will be stratified for UC, CD and IBDU
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
- Medical history of proctocolectomy
- Use of biologic therapy other than vedolizumab within 8 weeks of enrolment
- Inability to give informed consent
Opzet
Deelname
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In overige registers
| Register | ID |
|---|---|
| NTR-new | NL6718 |
| NTR-old | NTR6897 |
| CCMO | NL59904.018.16 |
| OMON | NL-OMON55753 |