title: Detection of anti-drug antibodies using a bridging ELISA compared with radioimmunoassay in adalimumab-treated rheumatoid arthritis patients with random drug levels.
abstract: OBJECTIVE
  To determine the concordance between RIA and bridging ELISA at detecting anti-drug antibodies (ADAbs) in the context of random adalimumab levels and investigate the additional clinical utility of detecting ADAbs in RA patients who test ADAb positive by RIA and negative by ELISA.
  
  
  METHODS
  ADAb levels were determined using RIA and bridging ELISA in 63 adalimumab-treated RA patients (159 samples). Immunogenicity concordance was determined using receiver operating characteristic curves. To determine the additional clinical value provided by a positive RIA in the presence of negative ELISA, association between treatment response (ΔDAS28), adalimumab drug levels and ADAbs was evaluated longitudinally using generalized estimating equation.
  
  
  RESULTS
  Of the 60 RIA+samples (n = 31 patients), 19 (n = 10 patients) were also ELISA+, corresponding to 31.7% of samples. Area under the curve for detecting ADAbs using ELISA (compared with RIA) using receiver operating characteristic curves was 0.65 (95% CI: 0.59, 0.71); this increased to 0.91 (95% CI: 0.81, 0.99) if ADAbs were ⩾100 AU/ml using RIA. In RIA+/ELISA-patients, adalimumab levels were associated with ΔDAS28 over 12 months [regression coefficient: 0.098 (95% CI: 0.043, 0.15), P < 0.0001] and while ADAbs were significantly associated with drug level, they were not directly associated with ΔDAS28 over 12 months [β coefficient: 0.00083 (95% CI: -0.0038 to 0.0054), P = 0.72].
  
  
  CONCLUSIONS
  ADAbs were detected using ELISA more frequently when present in high titres as measured by RIA. In RIA+/ELISA-patients, only drug levels were significantly associated with treatment response. Although ADAbs were not independently associated with treatment response, they may be helpful in determining the aetiology of low drug levels.
authors: Arthritis Research UK Centre for Epidemiology, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.|Arthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
authors: Meghna
authors: M
authors: Jani
authors: Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University.|National Institute of Health Research Newcastle Biomedical Research Centre, Newcastle upon Tyne, UK.
authors: John D
authors: JD
authors: Isaacs
authors: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, National Institute of Health Research Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK.
authors: Ann W
authors: AW
authors: Morgan
authors: University College of Dublin School of Medicine and Medical Science, Dublin, Ireland.
authors: Anthony G
authors: AG
authors: Wilson
authors: Arthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.|NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
authors: Darren
authors: D
authors: Plant
authors: Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, University of Manchester, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.|National Institute of Health Research Manchester Musculoskeletal Biomedical Research Unit, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
authors: Kimme L
authors: KL
authors: Hyrich
authors: NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.|Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
authors: Hector
authors: H
authors: Chinoy
authors: NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK anne.barton@manchester.ac.uk.|Arthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
authors: Anne
authors: A
authors: Barton
mesh_terms: D000068879:Adalimumab / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D000906:Antibodies / Q000378:metabolism*; D018501:Antirheumatic Agents / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D011446:Prospective Studies; D011863:Radioimmunoassay
chemical_list: D000906:Antibodies; D018501:Antirheumatic Agents; D000068879:Adalimumab
keywords: ELISA; RIA; TNF-inhibitors; adalimumab; anti-TNF; anti-drug antibodies; drug levels; human anti-human antibodies; immunogenicity; therapeutic drug monitoring