BIODISTRIBUTION AND KINETICS OF RADIOLABELED INFLIXIMAB IN RESPONDERS AND NON-RESPONDERS TO TREATMENT OF RHEUMATOID ARTHRITIS

Background: Many patients with rheumatoid arthritis (RA) are currently successfully treated with infliximab; however, approximately 30% of the patients does not respond to infliximab treatment. It is important to elucidate the cause of non-responding in order to adjust or change the therapy. One of the postulated hypotheses of non-responding is fast clearance of infliximab due to development of infliximab-to-anti-infliximab antibody complexes.Objectives: To investigate the mechanism of non-responding to infliximab treatment and the role of human anti-chimeric antibodies (HACA''s) by using radiolabeled infliximab.Methods: Eight weeks following the last infusion of infliximab, two responders and two non-responders were infused with 10 mg 740 MBq Tc-99m-labeled infliximab and simultaneously with 3 mg/kg unlabeled infliximab. The infusion time was two hours. Blood samples were withdrawn prior to, during and after infusion for further analysis. Whole body and spot views of clinically inflamed joints were made directly after the infusion and 24 hours later.Results: The infusion could be safely administered to the two responders. However, a serious anaphylactic response was observed in one non-responder. The infusion in this patient was immediately discontinued (at 30 min). In this patient, a high level of HACA (2085 U/ml) was found. In addition, sucrose gradients of serum of this patient revealed antibody complexes of various sizes, including very large ones, at 30 minutes of infusion. HACA was also detected in the other non-responder (1056 U/ml) who experienced mild parasthesias around the mouth and a light pressure on the chest during a few minutes. High amounts of small antibody complexes were observed in this patient between 30 and 60 minutes of infusion. HACA levels in the two responders were respectively very low (82 U/ml) and not detectable. Whole body images of responders and one non-responder (the other non-responder could not be subjected to imaging due to the infusion reaction) showed predominant presence of radiolabeled infliximab in the blood pool up to 24 hr p.i. At 24 hr, uptake of radiolabeled infliximab was demonstrated in clinically inflamed joints. Relatively high liver uptake was found in the non-responder, which is most likely related to local accumulation of antibody complexes.Conclusion: The results of this study contribute to elucidate the mechanism of non-responding to infliximab treatment in RA patients. Presence of HACA and formation of anti-infliximab-infliximab complexes were found within 60 minutes of infliximab infusion in non-responders to therapy. Antibody complexes accumulated in liver tissue. High levels of HACA and formation of large antibody complexes resulted in a serious anaphylactic response in one non-responder.Citation: Ann Rheum Dis, volume 64, supplement III, year 2005, page 369Session: Diagnostics and imaging procedures