arrow-pointing-right-300x251Vedolizumab

 

Vedolizumab (VDZ) is a humanised monoclonal antibody that binds exclusively to the lymphocyte integrin α4β7. VDZ inhibits the interaction of α4β7-expressing cells with mucosal addressin cell adhesion molecule-1 on endothelial cells, thereby hampering the infiltration of the α4β7-expressing cells into the gastrointestinal mucosa and gut-associated lymphoid tissue. VDZ suppresses gut inflammation and has therefore been approved for the treatment of patients with moderate to severely ulcerative colitis (UC)and Crohn’s disease (CD). It has been shown that VDZ can induce clinical remission and improve the patient’s quality of life.

Diagnostic Value

A drug can only exert its pharmacologic effect when adequate concentrations are achieved in the circulation. The serum concentration of biologicals just before their next infusion, defined as trough concentration, has been used for therapeutic drug monitoring (TDM). Recent data on TDM have shown a positive relationship between VDZ trough serum concentrations and clinical outcomes in patients with UC and CD. TDM may therefore be very instrumental to optimize treatment.

The apDia Vedolizumab ELISA uses highly specific monoclonal antibodies developed at the KU Leuven. Anti-TNF drugs (like infliximab, adalimumab, golimumab) do not interfere with the measurement.

As an example of TDM, the use of VDZ trough concentration measurements in UC and CD is described.

Ulcerative colitis

VDZ is given at week 0, week 2 and week 6 (induction) and upon good clinical response at week 14, treatment is continued by infusions every 8 weeks (maintenance). The exposure-efficacy relationships of VDZ evaluated in GEMINI 1 revealed a positive exposure-response relationship for clinical remission, clinical response, and mucosal healing for VDZ induction therapy in UC. VDZ trough concentration measurements during or shortly after induction may thus be used to identify undertreated patients.

It has been demonstrated that higher VDZ concentrations are associated with deep remission in patients with UC on maintenance therapy. Thus, regularly checking VDZ trough concentrations during maintenance therapy may be useful to evaluate the VDZ treatment schedule.

Crohn’s Disease

VDZ is given at week 0, week 2 and week 6 (induction) and upon good clinical response at week 14, treatment is continued by infusions every 8 weeks (maintenance). The exposure-efficacy relationships of VDZ evaluated in GEMINI 2 and 3 revealed a modest positive exposure-response relationship. Clinical remission rates were higher at week 10 than at week 6 in both studies. The European Medicines Agency allows an additional dose at week 10 before assessment of an induction response at week 14.

Due to the dosing regimen, trough concentrations during induction at week 2, week 6, week 10 (CD) & 14 (CD) are higher compared to trough concentrations during maintenance when VDZ is given every 8 weeks.

Immunogenicity

Secondary loss of response is often due to the development of anti-drug antibodies. The immunogenicity rate during treatment with VDZ is very low (4%).

Principle of the Vedolizumab ELISA

The apDia Vedolizumab ELISA uses highly specific monoclonal antibodies – clones 6F3 and 6E6, developed at the KU Leuven.

Microtiterstrips coated with anti-vedolizumab monoclonal antibody clone 6F3 are incubated with calibrators, controls and diluted patient samples. During this incubation step VDZ is captured specifically by the antibodies on the solid phase.  After removal of the unbound serum proteins by a washing procedure, the antigen-antibody complex in each well is detected with specific peroxidase-conjugated monoclonal antibody (clone 6E6) directed to VDZ.
After removal of the unbound conjugate, the strips are incubated with a chromogenic solution containing tetramethylbenzidin and hydrogen peroxide: a blue colour develops in proportion to the amount of immunocomplex bound to the wells of the strips.  The enzymatic reaction is stopped by the addition of 0.5M H2SO4 and the absorbance values at 450 nm are determined.
A standard curve is obtained by plotting the absorbance values versus the corresponding calibrator values. The concentration of VDZ in patient samples is determined by interpolation from the calibration curve.