title: Influence of immunogenicity on the efficacy of long-term treatment with infliximab in rheumatoid arthritis.
abstract: OBJECTIVE
  To analyse the clinical relevance of the production of anti-infliximab antibodies (anti-infliximab Abs) in patients with RA undergoing infliximab treatment over a prolonged period of time.
  
  
  METHODS
  Clinical characteristics, serum trough infliximab and antibody levels were evaluated in 85 RA patients treated with infliximab for a median of 4.42 (interval 0.4-10.2) years. DAS in 28 joints (DAS-28), EULAR response criteria and survival of treatment were assessed at 3 time points (6 months, 12 months and >4 years).
  
  
  RESULTS
  Antibodies against infliximab were detected in 28 (32.9%) patients and were present in all EULAR non-responder patients. Antibody levels were higher in EULAR non-responders throughout the study period (P = 0.05 at 6 months, P = 0.02 at 1 year, P = 0.003 at >4 years) compared with EULAR (good and moderate) responders. Nine (10.5%) patients, all of them with high-serum anti-infliximab Ab levels, developed infusion-related reactions. Patients with anti-infliximab Abs more often required increased infliximab doses (51.7%) (P = 0.032) and median survival time on treatment was shorter (4.15 vs 8.89 years) (P = 0.0006). MTX co-therapy was not associated with lower proportion of anti-infliximab Ab-positive patients, but those receiving both infliximab and MTX had lower levels of anti-infliximab Abs (P = 0.073) and longer survival (P = 0.015) on treatment.
  
  
  CONCLUSIONS
  The formation of anti-infliximab Abs during treatment with infliximab is associated with a loss of clinical response, the appearance of infusion reactions and discontinuation of treatment.
authors.affiliation: Immunology Unit, Hospital La Paz, Paseo de La Castellana 261, 28046 Madrid, Spain. dpascual.hulp@salud.madrid.org
authors.forename: Dora
authors.initials: D
authors.lastname: Pascual-Salcedo
authors.forename: Chamaida
authors.initials: C
authors.lastname: Plasencia
authors.forename: Susana
authors.initials: S
authors.lastname: Ramiro
authors.forename: Laura
authors.initials: L
authors.lastname: Nuño
authors.forename: Gema
authors.initials: G
authors.lastname: Bonilla
authors.forename: Daniel
authors.initials: D
authors.lastname: Nagore
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Ruiz Del Agua
authors.forename: Antonio
authors.initials: A
authors.lastname: Martínez
authors.forename: Lucien
authors.initials: L
authors.lastname: Aarden
authors.forename: Emilio
authors.initials: E
authors.lastname: Martín-Mola
authors.forename: Alejandro
authors.initials: A
authors.lastname: Balsa
mesh_terms: D000906:Antibodies / Q000097:blood; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000097:blood / Q000276:immunology; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000097:blood / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D004359:Drug Therapy, Combination; D004361:Drug Tolerance / Q000276:immunology; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D000069285:Infliximab; D008727:Methotrexate