Early Biomarkers in Circulating α 4β7 + T Cells to Predict Response to Vedolizumab in Inflamatory Bowel Disease Patients.
Status:
Completed
Trial end date:
2019-02-01
Target enrollment:
Participant gender:
Summary
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.