title: The formation of autoantibodies and antibodies to TNF-α blocking agents in relation to clinical response in patients with ankylosing spondylitis.
abstract: OBJECTIVE
  To investigate the influence of antibody formation to TNF-α blocking agents on the clinical response in AS patients treated with infliximab (IFX), etanercept (ETA), or adalimumab (ADA), and to investigate the development of ANA, ANCA, and anti-dsDNA antibodies in association with the formation of antibodies to TNF-α blocking agents.
  
  
  METHODS
  Consecutive AS outpatients with active disease who started treatment with IFX (n=20), ETA (n=20), or ADA (n=20) were included in this longitudinal observational study. Clinical data were collected prospectively at baseline and after 3, 6, and 12 months of anti-TNF-α treatment. At the same time points, serum samples were collected. In these samples, antibodies to TNF-α blocking agents, serum TNF-α blocker levels, and ANA, ANCA, and anti-dsDNA antibodies were measured retrospectively.
  
  
  RESULTS
  Anti-IFX, anti-ETA, and anti-ADA antibodies were induced in 20%, 0%, and 30% of patients, respectively. Although ANA, ANCA, and anti-dsDNA antibodies were detected during anti-TNF-α treatment, no significant association was found between the presence of these autoantibodies and the formation of antibodies to TNF-α blocking agents. Patients with anti-IFX or anti-ADA antibodies had significantly lower serum TNF-α blocker levels compared to patients without these antibodies. Furthermore, significant negative correlations were found between serum TNF-α blocker levels and assessments of disease activity.
  
  
  CONCLUSIONS
  This study indicates that antibody formation to IFX or ADA is related to a decrease in efficacy and early discontinuation of anti-TNF-α treatment in AS patients. Furthermore, autoantibody formation does not seem to be associated with antibody formation to TNF-α blocking agents.
authors.affiliation: Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands. s.arends@int.umcg.nl
authors.forename: S
authors.initials: S
authors.lastname: Arends
authors.forename: H R
authors.initials: HR
authors.lastname: Lebbink
authors.forename: A
authors.initials: A
authors.lastname: Spoorenberg
authors.forename: L B
authors.initials: LB
authors.lastname: Bungener
authors.forename: C
authors.initials: C
authors.lastname: Roozendaal
authors.forename: E
authors.initials: E
authors.lastname: van der Veer
authors.forename: P M
authors.initials: PM
authors.lastname: Houtman
authors.forename: E N
authors.initials: EN
authors.lastname: Griep
authors.forename: P C
authors.initials: PC
authors.lastname: Limburg
authors.forename: C G M
authors.initials: CG
authors.lastname: Kallenberg
authors.forename: G J
authors.initials: GJ
authors.lastname: Wolbink
authors.forename: E
authors.initials: E
authors.lastname: Brouwer
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000276:immunology / Q000627:therapeutic use*; D001323:Autoantibodies / Q000276:immunology*; D000068800:Etanercept; D005260:Female; D006304:Health Status; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000627:therapeutic use; D000069285:Infliximab; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000627:therapeutic use; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001323:Autoantibodies; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept