title: Detection of adalimumab and anti-adalimumab antibodies in patients with rheumatoid arthritis: a comprehensive overview of methodology pitfalls and benefits.
abstract: About a third of patients with rheumatoid arthritis treated with adalimumab may develop anti-adalimumab antibodies. Anti-adalimumab antibodies are associated with reduced drug levels, loss of drug efficacy, clinical non-response and an increased risk of adverse effects. In case of suspected drug failure and in order to better define clinical efficacy, adalimumab as well as anti-adalimumab antibodies levels should be monitored. Sandwich or indirect enzyme-linked immunoassay is most commonly used for determining adalimumab, while bridging ELISA and antigen-binding test are most useful for determining anti-adalimumab antibodies. Most current assays cannot detect antibodies complexed with the adalimumab; however, methods for dissociation of the complexes using acid/temperature have been developed. The aim of this review is to report on the latest methodology for detecting adalimumab and anti-ADL antibodies, benefits of their detections in clinical practice, as well as expose problematic issues, such as different analytical sensitivity and specificity, standardization and validation. The main problem in measuring adalimumab or anti-ADL antibodies is high drug sensitivity, which can result in false-negative anti-ADL antibodies. Therefore, drug-tolerant assays have been developed. Cell-based assays, such as the reporter gene assay, are recommended for detection of functionally active adalimumab and their neutralizing anti-ADL antibodies.
authors.affiliation: Department of Rheumatology, University Medical Centre-Ljubljana, Vodnikova 62, 1000, Ljubljana, Slovenia.
authors.forename: Manca
authors.initials: M
authors.lastname: Ogrič
authors.affiliation: Department of Rheumatology, University Medical Centre-Ljubljana, Vodnikova 62, 1000, Ljubljana, Slovenia.
authors.forename: Matic
authors.initials: M
authors.lastname: Terčelj
authors.affiliation: Department of Rheumatology, University Medical Centre-Ljubljana, Vodnikova 62, 1000, Ljubljana, Slovenia.
authors.forename: Sonja
authors.initials: S
authors.lastname: Praprotnik
authors.affiliation: Department of Rheumatology, University Medical Centre-Ljubljana, Vodnikova 62, 1000, Ljubljana, Slovenia.|Faculty of Medicine, University of Ljubljana, 1000, Ljubljana, Slovenia.
authors.forename: Matija
authors.initials: M
authors.lastname: Tomšič
authors.affiliation: Department of Rheumatology, University Medical Centre-Ljubljana, Vodnikova 62, 1000, Ljubljana, Slovenia.|Chair of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, 1000, Ljubljana, Slovenia.
authors.forename: Borut
authors.initials: B
authors.lastname: Božič
authors.affiliation: Department of Rheumatology, University Medical Centre-Ljubljana, Vodnikova 62, 1000, Ljubljana, Slovenia.|Natural Sciences and Information Technologies, Faculty of Mathematics, University of Primorska, 6000, Koper, Slovenia.
authors.forename: Snezna
authors.initials: S
authors.lastname: Sodin-Semrl
authors.affiliation: Department of Rheumatology, University Medical Centre-Ljubljana, Vodnikova 62, 1000, Ljubljana, Slovenia. sasa.cucnik@guest.arnes.si.|Chair of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, 1000, Ljubljana, Slovenia. sasa.cucnik@guest.arnes.si.
authors.forename: Saša
authors.initials: S
authors.lastname: Čučnik
mesh_terms: D000068879:Adalimumab / Q000097:blood / Q000276:immunology* / Q000627:therapeutic use; D000906:Antibodies / Q000097:blood*; D018501:Antirheumatic Agents / Q000097:blood / Q000276:immunology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007118:Immunoassay / Q000379:methods
chemical_list: D000906:Antibodies; D018501:Antirheumatic Agents; D000068879:Adalimumab
keywords: Adalimumab; Anti-drug antibodies; Inflammatory autoimmune diseases; Methodology; Rheumatoid arthritis; TNF-α inhibitors