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Imaging and serum analysis of immune complex formation of radiolabelled infliximab and anti-infliximab in responders and non-responders to therapy for rheumatoid arthritis
  1. C J van der Laken1,
  2. A E Voskuyl1,
  3. J C Roos2,
  4. M Stigter van Walsum3,
  5. E R de Groot4,
  6. G Wolbink4,
  7. B A C Dijkmans1,
  8. L A Aarden4
  1. 1Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands
  2. 2Department of Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands
  3. 3Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands
  4. 4Sanquin Research at CLB and Landsteiner Laboratory and Academical Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
  1. Correspondence to:
    C J van der Laken
    Department of Rheumatology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands; j.vanderlaken{at}vumc.nl

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.

Conclusion: 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.

  • HACA, human anti-chimeric antibody
  • TNF, tumour necrosis factor

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Footnotes

  • Competing interests: None.

  • Published Online First 22 June 2006

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