title: The frequency of anti-infliximab antibodies in patients with rheumatoid arthritis treated in routine care and the associations with adverse drug reactions and treatment failure.
abstract: OBJECTIVE
  To investigate the frequency of anti-infliximab antibodies in patients with RA and the associations with adverse drug reactions and treatment failure.
  
  
  METHODS
  Based on the DANBIO registry, patients with RA who initiated treatment with infliximab at Hvidovre Hospital between 2000 and 2008 and had available serum samples were identified. The patients were followed for 52 weeks. Anti-infliximab antibodies were determined prior to infusion at baseline and during follow-up (weeks 2, 6, 14 and 52 or at withdrawal) using the IMPACT indirect assay (Roche Diagnostics) and merged with clinical data prospectively registered in the DANBIO registry.
  
  
  RESULTS
  A total of 218 patients with RA were included (80% females, median age 56 years, disease duration 10 years, 65% RF positive, median DAS28 = 5.0). During the 52-week follow-up, 28 patients (13%) withdrew due to adverse events and 50 (23%) due to treatment failure. Antibodies were detected in 118 patients (54%) during follow-up. Patients with detectable anti-infliximab antibodies after 6 weeks had an increased risk of adverse drug reactions [hazard ratio (HR) = 5.06, 95% CI 2.36, 10.84; P < 0.0001] compared with patients without anti-infliximab antibodies. Similar results were observed in patients with anti-infliximab antibodies after 14 weeks (HR = 3.30, 95% CI 1.56, 6.99; P = 0.0009). Patients with detectable anti-infliximab antibodies during the 52-week follow-up were less likely to achieve sustained minimal disease activity and remission.
  
  
  CONCLUSIONS
  Early anti-infliximab antibody formation increased the risk of adverse drug reactions, including infusion reactions. Anti-infliximab antibody formation during the 52-week follow-up decreased the likelihood of minimal disease activity and remission in patients with RA treated in routine care.
authors: Department of Medicine, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730 Herlev, Denmark. krintel@sophine.dk
authors: Sophine B
authors: SB
authors: Krintel
authors: Veit Peter
authors: VP
authors: Grunert
authors: Merete L
authors: ML
authors: Hetland
authors: Julia S
authors: JS
authors: Johansen
authors: Matthias
authors: M
authors: Rothfuss
authors: Giuseppe
authors: G
authors: Palermo
authors: Laurent
authors: L
authors: Essioux
authors: Ursula
authors: U
authors: Klause
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D012042:Registries; D012307:Risk Factors; D017211:Treatment Failure; D016312:Treatment Refusal; D055815:Young Adult
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D000069285:Infliximab
keywords: DANBIO registry; adverse drug reactions; anti-TNF therapy; drug response; infliximab; neutralizing antibodies; pharmacological biomarkers; rheumatoid arthritis; treatment failure