Ulcerative Colitis
Conditions
Brief summary
A case-control study to evaluate the immunoinflammatory effect of prior exposure to anti-TNF therapy in patients with ulcerative colitis starting vedolizumab therapy
Detailed description
Inflammatory bowel disease (IBD)- ulcerative colitis (UC) and Crohn's disease (CD)- are chronic conditions of the gastrointestinal tract. Treatment generally consists of immunosuppression to modify the dysregulated immune responses. Vedolizumab, an inhibitor of α4β7, is a highly effective therapy for treating IBD, that minimized adverse effects through its gut selective inhibition of lymphocyte trafficking. However, the mechanism of action remains incompletely characterized especially in those previously treated to other biologics and why some patients are either vedolizumab non-responders or fail to respond over time. We would like to address the question whether anti-TNF non-responders as well as those that either do not respond or fail overtime to respond to vedolizumab identifies a specific population with difficult to treat disease that have alternate trafficking patterns and whether prior exposure to anti-TNF alters the mucosal immune responses, and/or trafficking patterns when compared to anti-TNF naive patients that may help explain impaired response to vedolizumab induction therapy.
Interventions
DRUGVedolizumab
standard vedolizumab induction (300mg IV at week 0, 2, 6)
Sponsors
Takeda
University of Western Ontario, Canada
University of California, San Diego
Stanford University
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* adult patients (\>18 years old) * clinical diagnosis of inflammatory bowel disease (Ulcerative Colitis) * clinical indication for biologic therapy * naive or failed anti-TNF therapy previously
Exclusion criteria
* patients allergic or intolerant to vedolizumab, * past use of vedolizumab; * patient unable to give consent to enter the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Analysis of blood and tissue leukocytes (T cells, B cells and Dendritic cells) | changes from enrollment to end of treatment (week 14) | Analysis of blood and tissue leukocytes (T cells, B cells and Dendritic cells) in patients with and without prior anti-TNF exposure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Analysis of the serum and tissue concentrations of inflammatory markers (interleukins) | changes from enrollment to end of treatment (week 14) | Analysis of the serum and tissue concentrations of inflammatory markers (interleukins) in vedolizumab responders versus non-responders |
| Analysis of the serum and tissue concentrations of vedolizumab | changes from enrollment to end of treatment (week 14) | Analysis of the serum and tissue concentrations of vedolizumab in patients with and without prior anti-TNF exposure |
Countries
Canada, United States
Outcome results
None listed