Comparison of the ELISA and ECL Assay for Vedolizumab Anti-drug Antibodies: Assessing the Impact on Pharmacokinetics and Safety Outcomes of the Phase 3 GEMINI Trials.

The AAPS Journal
Timothy WyantMaria Rosario

Abstract

Vedolizumab immunogenicity has been assessed using an enzyme-linked immunosorbent assay (ELISA) with a ~ 0.5 μg/mL drug interference, which may underestimate on-drug immunogenicity. We aimed to compare immunogenicity results between ELISA and the new drug-tolerant electrochemiluminescence (ECL) assay (and the two versions of neutralizing assays, drug-sensitive versus drug-tolerant). The ECL assay drug tolerance is ~ 100 times higher than that of the ELISA (≥ 50 μg/mL vs. 0.5 μg/mL with a 500 ng/mL positive control), and assay sensitivity is < 5 ng/mL for both assays. Vedolizumab immunogenicity was assessed in 2000 GEMINI 1 and 2 patients originally tested by ELISA and retested by ECL assay. Anti-drug antibody (ADA) impact on infusion-related reactions and pharmacokinetics (PK) was examined using descriptive statistics and population PK analyses. By ECL assay, 6% (86/1427) of patients treated with vedolizumab as induction and maintenance therapy tested ADA-positive. Of these, 20 patients were persistently positive and 56 had neutralizing antibodies. By ELISA, 4% (56/1434) of these patients were ADA-positive, 9 were persistently positive, and 33 had neutralizing antibodies. Among 61 patients with infusion-related reactions, 6 (10...Continue Reading

References

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Aug 24, 2013·The New England Journal of Medicine·Brian G FeaganUNKNOWN GEMINI 1 Study Group
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Jun 17, 2018·Mucosal Immunology·Sudarshan ParamsothyJean-Frederic Colombel

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
ELISA
acid dissociation
Assay
enzyme-linked

Clinical Trials Mentioned

NCT00783718
NCT00783692
NCT01224171

Software Mentioned

GEMINI
R
Nonlinear Mixed Effects Modelling ( NONMEM® )

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