title: Generation and characterization of a unique panel of anti-adalimumab specific antibodies and their application in therapeutic drug monitoring assays.
abstract: A number of assays are currently available to support therapeutic drug monitoring of adalimumab. A complete characterization of the assays and comparison of different assays has not been performed. The aim of this study, therefore, is to generate and characterize of a panel of monoclonal antibodies towards adalimumab (MA-ADM); to use this panel to develop novel assays to determine adalimumab concentrations; to assess the impact of tumor necrosis factor (TNF) and (non-)neutralizing antibodies on adalimumab detection and to compare the performance of assays. In total, ten specific MA-ADM were generated of which four revealed a neutralizing potency of >78%. At least six different clusters were identified using principal component analysis. MA-ADM40D8 was selected as detecting antibody to determine adalimumab in the TNF-coated ELISA (A) and the MA-ADM28B8/MA-ADM40D8 antibody pair was chosen for use in the MA-coated ELISA (B). The impact of TNF and (non-) neutralizing antibodies was similar in both ELISAs. Finally, serum samples of adalimumab-treated Crohn's disease patients were collected and used for an external validation using the assay of Sanquin (C) and the apDia kit (D). All adalimumab assays showed excellent Pearson correlation: r=0.96 for A versus B, 0.96 for A versus C, 0.94 for A versus D, 0.97 for B versus C, 0.95 for B versus D and 0.94 for C and D. The excellent agreement with the two commercially available ELISAs allows harmonization of treatment algorithms in and between different hospitals/infusion centers.
authors.affiliation: Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Sumin
authors.initials: S
authors.lastname: Bian
authors.affiliation: Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Thomas Van
authors.initials: TV
authors.lastname: Stappen
authors.affiliation: Department of Gastroenterology, AZ Delta, Roeselare, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Baert
authors.affiliation: Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Griet
authors.initials: G
authors.lastname: Compernolle
authors.affiliation: Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Els
authors.initials: E
authors.lastname: Brouwers
authors.affiliation: Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Tops
authors.affiliation: Sanquin Diagnostics Services, Amsterdam, The Netherlands.
authors.forename: Annick de
authors.initials: Ad
authors.lastname: Vries
authors.affiliation: Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Theo
authors.initials: T
authors.lastname: Rispens
authors.affiliation: Division of Mechatronics, Biostatistics and Sensors (MeBioS), KU Leuven, Leuven, Belgium.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Lammertyn
authors.affiliation: Department of Gastroenterology, University hospitals Leuven, Leuven, Belgium.
authors.forename: Séverine
authors.initials: S
authors.lastname: Vermeire
authors.affiliation: Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium. Electronic address: ann.gils@pharm.kuleuven.be.
authors.forename: Ann
authors.initials: A
authors.lastname: Gils
mesh_terms: D000068879:Adalimumab / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D003429:Cross Reactions; D016903:Drug Monitoring; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D009500:Neutralization Tests; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab
keywords: Adalimumab; Antibodies; Monoclonal; Therapeutic drug monitoring; Tumor necrosis factor-alpha