title: Differential effect of drug interference in immunogenicity assays.
abstract: The presence of anti-drug antibodies (ADA) in adalimumab-treated patients is associated with reduced serum adalimumab levels and a lower clinical response. Currently, there is no standard for measurement of anti-drug antibodies and many factors influence the results. Consequently, the incidence of ADA as reported in different studies varies considerably. Here we investigated the differential effect of drug interference in two common types of assays used to measure anti-adalimumab: an antigen binding test (ABT) and a more often-used bridging elisa. We measured ADA to adalimumab in a cohort of 216 rheumatoid arthritis patients treated with adalimumab for 28 weeks. Only 15 samples (7%) were positive in the bridging elisa, compared to 29 (13%) in the ABT, despite the fact that the bridging elisa was the most sensitive assay. Furthermore, in an ABT specific for IgG4, 48 samples (22%) were found positive. The bridging elisa was found to detect only the bivalent form of (drug-specific) IgG4, resulting in an underestimation of ADA levels. However, the predominant reason for the different outcomes of these assays was a differential susceptibility to drug interference. In particular, the bridging elisa only detected ADA in the absence of detectable amounts of circulating adalimumab and is therefore not suited for measurement of ADA in complex with the drug. In summary, we showed that a bridging elisa is susceptible to drug interference and typically measures ADA only in absence of detectable drug levels.
authors.affiliation: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory AMC, Amsterdam, The Netherlands.
authors.forename: Margreet H
authors.initials: MH
authors.lastname: Hart
authors.forename: Henk
authors.initials: H
authors.lastname: de Vrieze
authors.forename: Diana
authors.initials: D
authors.lastname: Wouters
authors.forename: Gerrit-Jan
authors.initials: GJ
authors.lastname: Wolbink
authors.forename: Joep
authors.initials: J
authors.lastname: Killestein
authors.forename: Els R
authors.initials: ER
authors.lastname: de Groot
authors.forename: Lucien A
authors.initials: LA
authors.lastname: Aarden
authors.forename: Theo
authors.initials: T
authors.lastname: Rispens
mesh_terms: D000068879:Adalimumab; D000893:Anti-Inflammatory Agents / Q000276:immunology* / Q000627:therapeutic use; D000888:Antibodies, Anti-Idiotypic / Q000097:blood / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D015331:Cohort Studies; D006801:Humans; D007118:Immunoassay / Q000379:methods* / Q000592:standards; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D011446:Prospective Studies
chemical_list: D000893:Anti-Inflammatory Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D000068879:Adalimumab