Clinical trial NCT02423512: The Impact of Anti-TNF Exposure on Vedolizumab Effectiveness
Official title: The Impact of Anti-TNF Exposure on Vedolizumab Effectiveness: A Biomarker Study.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Inflammatory Bowel Disease
Crohn's Disease
Ulcerative Colitis
Keywords: Inflammatory Bowel Diseases
Vedolizumab
Ulcerative Colitis
Crohn's Disease
MADCAM1
integrin alpha4beta7
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2015-04-22
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Male and female adults with a diagnosis of inflammatory bowel disease 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

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: biomarker MAdCAM-1
timeFrame: baseline and week 14
Secondary outcomes:
measure: biomarker alpha 4 beta 7
timeFrame: baseline and week 14
measure: TNF levels
timeFrame: baseline and week 14
measure: mucosal drug concentration
timeFrame: week 14
measure: mucosal drug concentration
timeFrame: week 30
measure: vedolizumab drug concentration
timeFrame: week 14
measure: vedolizumab drug concentration
timeFrame: week 30
Other outcomes:
Locations:
city: New York
country: United States
facility: Susan and Leonard Feinstein Inflammatory Bowel Disease Center
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Marla C. Dubinsky, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sandborn WJ, Feagan BG, Rutgeerts P, Hanauer S, Colombel JF, Sands BE, Lukas M, Fedorak RN, Lee S, Bressler B, Fox I, Rosario M, Sankoh S, Xu J, Stephens K, Milch C, Parikh A; GEMINI 2 Study Group. Vedolizumab as induction and maintenance therapy for Crohn's disease. N Engl J Med. 2013 Aug 22;369(8):711-21. doi: 10.1056/NEJMoa1215739.
citation: Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel JF, Sandborn WJ, Van Assche G, Axler J, Kim HJ, Danese S, Fox I, Milch C, Sankoh S, Wyant T, Xu J, Parikh A; GEMINI 1 Study Group. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013 Aug 22;369(8):699-710. doi: 10.1056/NEJMoa1215734.
citation: Sandborn WJ, Colombel JF, Enns R, Feagan BG, Hanauer SB, Lawrance IC, Panaccione R, Sanders M, Schreiber S, Targan S, van Deventer S, Goldblum R, Despain D, Hogge GS, Rutgeerts P; International Efficacy of Natalizumab as Active Crohn's Therapy (ENACT-1) Trial Group; Evaluation of Natalizumab as Continuous Therapy (ENACT-2) Trial Group. Natalizumab induction and maintenance therapy for Crohn's disease. N Engl J Med. 2005 Nov 3;353(18):1912-25. doi: 10.1056/NEJMoa043335.
citation: Sands BE, Feagan BG, Rutgeerts P, Colombel JF, Sandborn WJ, Sy R, D'Haens G, Ben-Horin S, Xu J, Rosario M, Fox I, Parikh A, Milch C, Hanauer S. Effects of vedolizumab induction therapy for patients with Crohn's disease in whom tumor necrosis factor antagonist treatment failed. Gastroenterology. 2014 Sep;147(3):618-627.e3. doi: 10.1053/j.gastro.2014.05.008. Epub 2014 May 21.
citation: Arjis I, De Hertogh G, Machiels K, et al. Mucosal gene expression of cell adhesion molecules, chemokines, and chemokine receptors in patients with inflammatory bowel disease before and after infliximab treatment. American Journal of Gastroenterology. April 2011;106:748-761 Biancheri P, Di Sabatino A, Rovedatti L, et al. Effect of tumor necrosis factor-alpha blockade on mucosal addressin cell-adhesion molecule-1 in Crohn's disease. Inflammatory Bowel Disease. Feb 2013;19(2):259-264.