Drug interference in immunogenicity assays depends on valency

Theo Rispens, Margreet H. Hart, Pleuni Ooijevaar-de Heer, Astrid van Leeuwen, Anke Vennegoor, Joep Killestein, Gerrit-Jan Wolbink, Desiree van der Kleij

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Abstract

Direct comparison of immunogenicity data is hampered by differential drug interference in different assay formats. In this paper we identify a drug-related factor that influences the extent of drug interference. We systematically investigated the influence of drug valency of different antibody-derived biologicals on the drug interference, using mono- and bivalent formats of adalimumab as a model system. Our results indicate that compared to regular bivalent antibodies, antibody-derived drugs that are monovalent result in less drug interference. Two real-life examples were examined: natalizumab, an IgG4 antibody that becomes effectively monovalent in vivo due to Fab arm exchange, and certolizumab pegol, a pegylated Fab fragment. For both drugs it was demonstrated that drug interference is less pronounced in an antigen-binding test compared to similar assays for other therapeutic antibodies. When comparing immunogenicity data obtained for different biologicals this phenomenon should be taken into account
Original languageEnglish
Pages (from-to)179-185
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume85
DOIs
Publication statusPublished - 2013

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