Early Biomarkers in Circulating α 4β7 + T Cells to Predict Response to Vedolizumab in Inflamatory Bowel Disease Patients.

EARLY BIOMARKERS IN CIRCULATING α 4β7+ T CELLS TO PREDICT RESPONSE TO VEDOLIZUMAB IN INFLAMMATORY BOWEL DISEASE PATIENTS

Background: Infiltration of GI by T lymphocytes is a pathogenic mechanism both in ulcerative colitis (UC) and in Crohn's disease (CD). Vedolizumab (VDZ) is a humanized monoclonal antibody binding with high affinity to α4β7 integrin blocking α4β7+-MAdCAM-1 interaction, hence blocking a key step in GI lymphocytes T infiltration. VDZ has demonstrated a therapeutic effect in UC and CD. Investigators still lack of adequate biomarkers to predict clinical response to biological treatments, specially avoiding invasive procedures.

Objective: Study whether circulating CD4+ and CD8+ α4β7+ memory T lymphocytes and some of their surface markers might be molecular markers of response to VDZ treatment in patients with UC and CD.

Methods: Prospective (pilot) study including 24 adult IBD patients (12 UC patients and 12 CD patients (patients with fistulizing perianal disease will be excluded) with active disease and prior failure to anti-TNFα treatments starting treatment with VDZ. They will received VDZ in standard induction (300mg intravenously, 0-2-6 weeks) and maintenance schemes (300mg intravenously, every 8 weeks).

Epidemiological and clinical data from every patient will be recorded prospectively. Disease activity at weeks 0, 2, 6 and 14 weeks will be evaluated through validated clinical scores, biological parameters and fecal biomarkers.

At week 14 response to the treatment will be evaluated by ileocolonoscopy or enteroMRI.

Peripheral blood will be obtained from every patient at baseline, before the third infusion of VDZ (6th week) and before the first maintenance dose (14th week).

Blood lymphocytes will be isolated and multicolor flow cytometry will be performed on stored circulating memory T cells.

Percentage and absolute values of circulating CD4+ and CD8+ α4β7+ memory T lymphocytes as well as several surface markers related to their activation state (HLA-DR, CD25), Th17 phenotype (IL23R, CCR6, intracellular IL17A) and Th1 phenotype (INFγ)will be assessed on α4β7+ memory T cells.

Study Overview

• Status: Completed
• Conditions: Inflammatory Bowel Disease
• Intervention / Treatment: Drug: Vedolizumab

• Study Type: Observational
• Enrollment (Actual): 24

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

24 adults with inflammatory bowel disease (12 Ulcerative colitis patients and 12 Chron Disease patients with active disease and prior failure to anti-TNFα treatments (inadequate response, loss of response, intolerance), starting treatment with Vedolizumab.

Description

Inclusion Criteria:

• Ulcerative colitis or Crohn's disease diagnosis established by Lennard-Jones criteria
• Clinically active disease confirmed by endoscopic or radiologic criteria Magnetic Resonance Image (MRI)
• >18 years of age
• Intolerant, refractory or secondary loss of response to anti-Anti-tumour necrosis factor (TNF) alfa treatment.

Exclusion Criteria:

• Crohn's disease with perianal disease
• Active Tuberculosis
• Current infections (including Clostridium difficile and Cytomegalovirus)
• History of cancer, including hematologic malignancy and solid tumours within 5 years before
• History of demyelinating disease
• Pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients treated with vedolizumab	Drug: Vedolizumab; Administration of intravenous Vedolizumab in inflammatory bowel disease patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Surface and Th17 phenotype markers in T lymphocytes as response predictors	From drug administration until 14 weeks.

Secondary Outcome Measures

Outcome Measure	Time Frame
Surface and Th17 phenotype markers in T lymphocytes as sustained remission predictors	From drug administration (week 14th) until 12 months.

Collaborators and Investigators

• Sponsor: Parc de Salut Mar

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): February 1, 2019
• Study Completion (Actual): February 1, 2019

Study Registration Dates

• First Submitted: March 14, 2016
• First Submitted That Met QC Criteria: March 14, 2016
• First Posted (Estimate): March 18, 2016

Study Record Updates

• Last Update Posted (Actual): February 28, 2019
• Last Update Submitted That Met QC Criteria: February 26, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases; Gastrointestinal Agents; Vedolizumab
• Other Study ID Numbers: FIM-VED-2016-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No