The Impact of Anti-TNF Exposure on Vedolizumab Effectiveness

Study Overview
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Brief Summary
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Vedolizumab is a new medication being used for the treatment of Crohn's disease and Ulcerative colitis. It works by blocking specific white blood cells (alpha 4-beta7 lymphocytes) from migrating to areas of inflammation in the gastrointestinal tract. Previous studies have shown that patients who have previous exposure to another type of medication for Crohn's disease and Ulcerative colitis (anti-TNF medications) do not respond to vedolizumab as well as those who have never been exposed. This study will investigate biologic markers in the blood and tissue the help identify possible reasons for this difference.

Detailed Description
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Patients will be enrolled in the study when they are selected to initiate vedolizumab therapy. Vedolizumab is an intravenous infusion given at increasing intervals. The first infusion of vedolizumab will be considered baseline. Patients may be enrolled at baseline or at colonoscopy prior to the first scheduled infusion of vedolizumab (pre-treatment visit). The standard induction protocol for vedolizumab consists of infusions at week 0 (baseline), week 2, and week 6. Vedolizumab, as per standard-of-care, is then continued at an interval of every 8 weeks following induction therapy. Vedolizumab treatment will be prescribed as per standard practice and will be prescribed regardless of participation in this study. Patients will not receive medication for the sole purpose of this research. Treatment decisions including timing of wash out period between anti-TNf and vedolizumab will be made by the subject's physician and not per the research protocol. There will not be a protocolized washout period for patients previously receiving anti-TNF therapy because treatment will be standard of care and per the directing physician. Standard of care laboratory tests will be performed by the clinical laboratory at Mount Sinai Hospital. All other measurements will be completed at Prometheus Therapeutics & Diagnostics in San Diego, California or at a Takeda identified lab for vedolizumab concentrations and antibodies.

Official Title
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The Impact of Anti-TNF Exposure on Vedolizumab Effectiveness: A Biomarker Study.

Conditions
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Inflammatory Bowel Disease, Crohn's Disease, Ulcerative Colitis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female adults with a diagnosis of inflammatory bowel disease Patients who will be started on vedolizumab therapy as clinically indicated and in discussion with their treating physician will be eligible. Patients will not be started on vedolizumab for the sole purpose of this study Exclusion Criteria: -Patients with prior exposure to vedolizumab or natalizumab

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Anti-TNF Exposure<br>Inflammatory Bowel Disease (IBD) patients scheduled to start vedolizumab therapy who have been previously exposed to anti-TNF therapy | |
| anti-TNF Naive<br>IBD patients scheduled to start vedolizumab therapy who have not been previously exposed to anti-TNF therapy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| biomarker MAdCAM-1 | change in biomarker MAdCAM-1 at week 14 as compared to baseline | baseline and week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| biomarker alpha 4 beta 7 | change in biomarker alpha 4 beta 7 at week 14 as compared to baseline | baseline and week 14 | 
| TNF levels | change in TNF levels at week 14 as compared to baseline | baseline and week 14 | 
| mucosal drug concentration | mucosal drug concentration in those undergoing colonoscopy | week 14 | 
| mucosal drug concentration | mucosal drug concentration in those undergoing colonoscopy | week 30 | 
| vedolizumab drug concentration | vedolizumab drug concentration in those patients scheduled for vedolizumab therapy | week 14 | 
| vedolizumab drug concentration | vedolizumab drug concentration in those patients scheduled for vedolizumab therapy | week 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's Disease, MADCAM1, integrin alpha4beta7, Inflammatory Bowel Diseases, Vedolizumab, Ulcerative Colitis