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P474 An enzyme-linked immunosorbent assay for therapeutic drug monitoring of vedolizumab

Berger C.1, Semmler J.1, Ruppert J.1, Schulze H.2, Armbruster F.-P.1, Dignass A.2,3, Stein J.*3,4

1Immundiagnostik AG, Bensheim, Germany 2Agaplesion Markus Krankenhaus, Frankfurt/Main, Germany 3Interdisciplinary Crohn Colitis Centre Rhein-Main, Frankfurt/Main, Germany 4DGD Clinics Sachsenhausen, Frankfurt/Main, Germany

Background

Vedolizumab (VLZ), an α4β7 integrin antagonist, is a therapeutic monoclonal antibody recently approved for use in moderate to severe ulcerative colitis (UC) and Crohn's disease (CD). Part of the interindividual differences in response to VLZ treatment may be explained by interindividual variability in pharmacokinetics.

Methods

Microtiter plates were coated with anti-VLZ specific monoclonal antibody. Samples diluted 1:200 were added on a microtiter plate for specific binding, and bound VLZ was detected using mouse anti-human immunoglobulin G1 (HRP-anti h IgG1). Trough serum concentrations of VLZ were analyzed in 86 samples of 21 adult UC patients and compared to concentrations measured by in-house developed LC-MS/MS assay (Christ et al., J Crohn's Colitis 2016, S1).

Results

The limit of quantification (LoQ) for VLZ determination in human serum samples was 0.0071 μg/mL. The intra-assay variation (n=20) was 8.57% for 9.55 μg/mL and 6.54% for 18.9 μg/mL. The inter-assay variation (n=40) was 7.10% for 28.5 μg/mL and 8.33% for 35.7 μg/mL. Linearity testing of the ELISA was performed by analysis of two serially diluted patient samples; the coefficients of variation (CV%) were below 8%. No false positive signals were detected in samples spiked with TNFα blockers (infliximab, adalimumab, golimumab). In the samples of patients treated with VLZ the trough level ranged from 0.02 to 71.01 μg/mL. VLZ results of ELISA and an in-house developed LC-MS/MS assay showed a correlation coefficient (r) of 0.96 (Fig. 1).

Figure 1

Conclusion

This newly developed ELISA method is rapid, accurate and reproducible, and may be useful for pharmacokinetic-pharmacodynamic studies, as well as in therapeutic drug monitoring of vedolizumab.