title: Influence of immunogenicity on the efficacy of longterm treatment of spondyloarthritis with infliximab.
abstract: BACKGROUND
  Infliximab (IFX) is a monoclonal antibody against tumour necrosis factor α that is effective for treating spondyloarthritis (SpA). However, after initial success of the drug some patients lose responsiveness or develop infusion reactions, which may be related to the development of antibodies against the drug.
  
  
  OBJECTIVE
  To investigate the clinical relevance of antibodies to infliximab (ATI) formation in patients with SpA undergoing IFX treatment over a prolonged period.
  
  
  METHODS
  94 patients with SpA treated with IFX from 1999 to 2010 were studied. Their clinical characteristics, serum trough IFX levels and ATI status were evaluated for a mean of 6.99 (95% CI:6.28 to 7.7) years. Clinical activity and improvement were measured using the Ankylosing Spondylitis Disease Activity Score (ASDAS): inactive <1.3, moderate ≥1.3 and <2.1, high ≥2.1-≤3.5, and very high >3.5 at three time points (6 months, 12 months and >4 years).
  
  
  RESULTS
  ATI were detected in 24 (25.5%) patients. The patients with ATI had higher ASDAS scores than those without ATI (2.55±0.89 vs 1.79±1.04, p=0.038 at 6 months; 1.95±0.67 vs 1.67±0.71, p=0.042 at 1 year; 2.52±0.99 vs 1.53±0.81, p=0.024 at >4 years). Eleven patients (12%) developed infusion-related reactions, and of these, ATI were present in eight patients (73%). The patients with infusion-related reactions had higher ATI titres (median 12 931 AU/ml, IQR 853-82 437) vs median 2454 AU/ml, IQR 449-7718, p=0.028) and shorter survival (4.25 years vs 8.19 years, p<0.001). ATI development occurred more frequently in the patients not receiving methotrexate (20/58 (34.5%) vs 4/36 (11.1%), p=0.011).
  
  
  CONCLUSIONS
  In patients with SpA treated with IFX, ATI formation is associated with a poor clinical response, the appearance of infusion reactions and the discontinuation of treatment.
authors.affiliation: La Paz University Hospital, Department of Rheumatology, Castellana 261, Madrid 28046, Spain. chamiplasencia@hotmail.com
authors.forename: Chamaida
authors.initials: C
authors.lastname: Plasencia
authors.forename: Dora
authors.initials: D
authors.lastname: Pascual-Salcedo
authors.forename: Laura
authors.initials: L
authors.lastname: Nuño
authors.forename: Gema
authors.initials: G
authors.lastname: Bonilla
authors.forename: Alejandro
authors.initials: A
authors.lastname: Villalba
authors.forename: Diana
authors.initials: D
authors.lastname: Peiteado
authors.forename: Jesús
authors.initials: J
authors.lastname: Díez
authors.forename: Daniel
authors.initials: D
authors.lastname: Nagore
authors.forename: Ainhoa Ruiz
authors.initials: AR
authors.lastname: del Agua
authors.forename: Rosario
authors.initials: R
authors.lastname: Moral
authors.forename: Emilio
authors.initials: E
authors.lastname: Martin-Mola
authors.forename: Alejandro
authors.initials: A
authors.lastname: Balsa
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000097:blood / Q000276:immunology*; D003156:Community Mental Health Services; D004351:Drug Resistance / Q000276:immunology; D005260:Female; D006801:Humans; D000069285:Infliximab; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012720:Severity of Illness Index; D025241:Spondylarthritis / Q000188:drug therapy* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab