title: Anti-therapeutic antibodies and their clinical impact in patients treated with the TNF antagonist adalimumab.
abstract: Patients treated with the TNF antagonist adalimumab develop anti-therapeutic antibodies (ATA), the prevalence of which varies depending on the assay used. Most assays are compromised due to the presence of adalimumab in the clinical samples. Our objective was to develop an antibody assay, applicable for clinical testing, which overcomes the limitation of therapeutic interference and to further determine the relationship between ATA development, adalimumab levels and disease activity in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS). Use of an electrochemiluminescence platform permitted development of fit-for-purpose immunoassays. Serum samples from patients, taken prior to and at 12 and 24weeks of treatment, were retrospectively analysed for levels of adalimumab and ATA. Overall, the antibody prevalence was 43.6% at 12weeks and 41% at 24weeks of treatment. Disruption of immune complexes by acid dissociation, a strategy often adopted for this purpose, only marginally increased the antibody prevalence to 48.7% and 46% at 12 and 24weeks respectively. We found that antibody formation was associated with decreasing levels of circulating adalimumab, but no direct effect on disease activity was evident as assessed using DAS28 for RA patients and BASDAI for PsA and AS patients. However, a negative correlation of free adalimumab trough levels with disease activity scores was observed. Data showed that adalimumab levels can serve as an indicator of ATA development which can then be confirmed by ATA testing. Monitoring of both therapeutic and antibodies should be considered during adalimumab therapy to allow clinicians to personalise treatments for maximal therapeutic outcomes.
authors.affiliation: Biotherapeutics Group, Cytokines and Growth Factor Section, National Institute for Biological Standards and Control, Medicines and Healthcare products Regulatory Agency, Blanche Lane, Potters Bar, Hertfordshire EN6 3QG, United Kingdom. Electronic address: Isabelle.Cludts@nibsc.org.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cludts
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Spinelli
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Morello
authors.affiliation: Biostatistics, National Institute for Biological Standards and Control, Medicines and Healthcare products Regulatory Agency, Blanche Lane, Potters Bar, Hertfordshire EN6 3QG, United Kingdom.
authors.forename: Jason
authors.initials: J
authors.lastname: Hockley
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Valesini
authors.affiliation: Biotherapeutics Group, Cytokines and Growth Factor Section, National Institute for Biological Standards and Control, Medicines and Healthcare products Regulatory Agency, Blanche Lane, Potters Bar, Hertfordshire EN6 3QG, United Kingdom.
authors.forename: Meenu
authors.initials: M
authors.lastname: Wadhwa
mesh_terms: D000068879:Adalimumab / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use*; D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D015535:Arthritis, Psoriatic / Q000188:drug therapy; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D055664:Electrochemical Techniques; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab
keywords: Adalimumab trough levels; Electrochemiluminescence assay; Immunogenicity; Neutralizing antibodies; TNF antagonist