title: Antibodies toward infliximab are associated with low infliximab concentration at treatment initiation and poor infliximab maintenance in rheumatic diseases.
abstract: BACKGROUND
  A proportion of patients receiving infliximab have antibodies toward infliximab (ATI), which are associated with increased risk of infusion reaction and reduced response to treatment. We studied the association of infliximab concentration at treatment initiation and development of ATI as well as the association of the presence of ATI and maintenance of infliximab.
  
  
  METHODS
  All patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) receiving infliximab beginning in December 2005 were retrospectively followed until January 2009 or until infliximab discontinuation. Trough serum infliximab and ATI concentrations were measured at each visit. The patients were separated into two groups: ATI(pos) if ATI were detected at least once during the follow-up period and ATI(neg) otherwise. Repeated measures analysis of variance was used to study the association of infliximab concentration at treatment initiation and the development of ATI. Maintenance of infliximab in the two groups was studied by using Kaplan-Meier curves.
  
  
  RESULTS
  We included 108 patients: 17 with RA and 91 with SpA. ATI were detected in 21 patients (19%). The median time to ATI detection after initiation of infliximab was 3.7 months (1.7 to 26.0 months). For both RA and SpA patients, trough infliximab concentration during the initiation period was significantly lower for ATI(pos) than ATI(neg) patients. RA patients showed maintenance of infliximab at a median of 19.5 months (5.0 to 31.0 months) and 12.0 months (2.0 to 24.0 months) for ATI(neg) and ATI(pos) groups, respectively (P = 0.08). SpA patients showed infliximab maintenance at a median of 16.0 months (3.0 to 34.0 months) and 9.5 months (3.0 to 39.0 months) for ATI(neg) and ATI(pos) groups, respectively (P = 0.20). Among SpA patients, those who were being treated concomitantly with methotrexate had a lower risk of developing ATI than patients not taking methotrexate (0 of 14 patients (0%) vs. 25 of 77 patients (32%); P = 0.03).
  
  
  CONCLUSIONS
  High concentrations of infliximab during treatment initiation reduce the development of ATI, and the absence of ATI may be associated with prolonged maintenance of infliximab. Thus, trough serum infliximab concentration should be monitored early in patients with rheumatic diseases.
authors.affiliation: Université François Rabelais de Tours, Centre National de la Recherche Scientifique UMR 6239 GICC, 3 rue des Tanneurs, F-37041 Tours Cedex 1, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Ducourau
authors.forename: Denis
authors.initials: D
authors.lastname: Mulleman
authors.forename: Gilles
authors.initials: G
authors.lastname: Paintaud
authors.forename: Delphine Chu
authors.initials: DC
authors.lastname: Miow Lin
authors.forename: Francine
authors.initials: F
authors.lastname: Lauféron
authors.forename: David
authors.initials: D
authors.lastname: Ternant
authors.forename: Hervé
authors.initials: H
authors.lastname: Watier
authors.forename: Philippe
authors.initials: P
authors.lastname: Goupille
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000097:blood / Q000276:immunology*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000097:blood / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005500:Follow-Up Studies; D006801:Humans; D000069285:Infliximab; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D012189:Retrospective Studies; D025241:Spondylarthritis / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D055815:Young Adult
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D000069285:Infliximab