Measuring Serum Vedolizumab and Vedolizumab Antibodies: Comparison of Commercial Assays with the Vedolizumab Clinical Development Assay

Abstract

Background: Vedolizumab (VDZ) is an anti-a 4 b 7 integrin monoclonal antibody approved for inflammatory bowel disease treatment. VDZ serum and antidrug antibody (ADA) concentrations may be used for treatment optimization. In this article, the results of 5 commercial assays (Grifols, Immundiagnostik, Progenika, Sanquin, and Theradiag) measuring VDZ concentration and ADA were compared with those of the reference assays used in VDZ clinical studies. Our findings will assist clinicians in interpreting commercial assay results in the context of VDZ clinical trial data.Methods: VDZ-treated patient samples were used to evaluate the agreement between commercial assays and the reference VDZ serum concentration assay, based on linear regression, Bland-Altman, and qualitative agreement analyses. VDZ ADAs were detected using qualitative assays. Specificity, selectivity, accuracy, and precision were assessed using serum samples from healthy donors or patients with IBD (VDZ serum concentration ,0.5 mcg/mL) spiked with VDZ, with/without other biologics (identical sample sets per assay).Results: All assays were specific and selective for VDZ. Overall, the commercial assay results for VDZ-spiked samples correlated well with those of the reference serum concentration assay (R 2 $ 0.98). Compared with the Immundiagnostik and Theradiag assays, the Grifols, Sanquin, and Progenika assays had the best reference assay agreement (based on regression analysis, Bland-Altman plots, and qualitative agreement [Cohen's kappa $0.92]). All immunogenicity assays detected VDZ ADAs; only the reference assay detected VDZ ADAs in the presence of 15 mcg/mL VDZ, advising caution with commercial ADA assays if VDZ is present.Conclusions: All 5 commercial assays are suitable for VDZ therapeutic monitoring and ADA testing. However, the absolute values from the reference assays and the different commercial assays were not comparable, indicating that the same assay must be used for repeated monitoring of VDZ serum concentrations.

Observational Study to Compare Biological Drug Concentration Quantification Techniques and Immunogenicity in Patients with Immune-Mediated Diseases

“…To date, we have not found any research about cVED quantification techniques other than ELISA. There are a few studies that compare different techniques to determine antibodies [32] or different ELISA tests [33], but in our study, vedolizumab ADAs were not determined. This could be due to the less experience that exists in the TDM of this drug compared to the others described in our work.…”

Therapeutic Drug Monitoring for Biologic and Small-Molecule Therapies for Inflammatory Bowel Disease

“…There are multiple methods for therapeutic drug monitoring, including enzyme-linked immunoassays (ELISAs), liquid chromatography and radioimmunoassay, with ELISA being the most common in commercial use [28][29][30][31][32]. The key components of these assays are summarised in Table 1.…”