title: Drug interference in immunogenicity assays depends on valency.
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.
authors: Sanquin Research, Amsterdam, The Netherlands; Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, The Netherlands. t.rispens@sanquin.nl
authors: Theo
authors: T
authors: Rispens
authors: Margreet H
authors: MH
authors: Hart
authors: Pleuni
authors: P
authors: Ooijevaar-de Heer
authors: Astrid
authors: A
authors: van Leeuwen
authors: Anke
authors: A
authors: Vennegoor
authors: Joep
authors: J
authors: Killestein
authors: Gerrit-Jan
authors: GJ
authors: Wolbink
authors: Desiree
authors: D
authors: van der Kleij
mesh_terms: D000068879:Adalimumab; D000906:Antibodies / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology*; D000917:Antibody Formation; D000068582:Certolizumab Pegol; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007158:Immunologic Techniques; D000069442:Natalizumab; D011092:Polyethylene Glycols
chemical_list: D000906:Antibodies; D061067:Antibodies, Monoclonal, Humanized; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D000069442:Natalizumab; D011092:Polyethylene Glycols; D000068879:Adalimumab; D000068582:Certolizumab Pegol
keywords: ABT; ADA; Anti-drug antibody (ADA); Bispecific antibody; Certolizumab; Drug interference; GSH; Natalizumab; anti-drug antibody; antigen binding test; reduced glutathione