title: Imaging and serum analysis of immune complex formation of radiolabelled infliximab and anti-infliximab in responders and non-responders to therapy for rheumatoid arthritis.
abstract: BACKGROUND
  Many patients with rheumatoid arthritis are currently successfully treated with infliximab (anti-tumour necrosis factor); however, about 30% of the patients do not respond to infliximab. One of the postulated hypotheses of not responding is the fast clearance of infliximab due to the development of infliximab-anti-infliximab complexes.
  
  
  OBJECTIVE
  To investigate the in vivo mechanism of not responding and the role of human anti-chimeric antibodies (HACAs) by using radiolabelled infliximab.
  
  
  METHODS
  Two responding and two non-responding patients with rheumatoid arthritis, infused with radiolabelled infliximab, were investigated by both imaging and serum analysis.
  
  
  RESULTS
  Images showed predominant presence of infliximab in blood up to 24 h, with a trend of faster blood clearance and of higher liver/spleen uptake in a non-responding patient. Clinically inflamed joints showed uptake of the drug. The HACA level in the non-responders was high (1641 and 1008 U/ml), but low or not detectable in responders. Sucrose gradients of serum showed antibody complexes in both non-responders. Various sizes of antibody complexes, including very large ones, were observed in a non-responder who developed a serious infusion reaction.
  
  
  CONCLUSIONS
  Formation of infliximab-anti-infliximab complexes were found in non-responders due to the presence of large amounts of HACA. This finding, supported by both imaging and serum analysis data, may explain failure of infliximab treatment.
authors.affiliation: Department of Rheumatology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. j.vanderlaken@vumc.nl
authors.forename: C J
authors.initials: CJ
authors.lastname: van der Laken
authors.forename: A E
authors.initials: AE
authors.lastname: Voskuyl
authors.forename: J C
authors.initials: JC
authors.lastname: Roos
authors.forename: M
authors.initials: M
authors.lastname: Stigter van Walsum
authors.forename: E R
authors.initials: ER
authors.lastname: de Groot
authors.forename: G
authors.initials: G
authors.lastname: Wolbink
authors.forename: B A C
authors.initials: BA
authors.lastname: Dijkmans
authors.forename: L A
authors.initials: LA
authors.lastname: Aarden
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D000936:Antigen-Antibody Complex / Q000032:analysis* / Q000276:immunology; D018501:Antirheumatic Agents / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D001323:Autoantibodies / Q000032:analysis / Q000097:blood; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D000069285:Infliximab; D007553:Isotope Labeling; D007596:Joints / Q000000981:diagnostic imaging / Q000378:metabolism; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011877:Radionuclide Imaging; D013154:Spleen / Q000000981:diagnostic imaging / Q000378:metabolism; D013667:Technetium; D017211:Treatment Failure; D051598:Whole Body Imaging
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D018501:Antirheumatic Agents; D001323:Autoantibodies; D007166:Immunosuppressive Agents; D013667:Technetium; D000069285:Infliximab