Pharmacokinetics and -Dynamics of Natalizumab after Cessation and at Different Dosing Intervals (P06.167)

Objective: To assess the pharmacokinetics and -dynamics after cessation of natalizumab and at different application intervals. Background Natalizumab, a humanized recombinant monoclonal antibody, is approved for the treatment of highly active relapsing-remitting multiple sclerosis. As decreased immune surveillance of the brain can cause progressive multifocal leukoencephalopathy (PML) during natalizumab treatment, treatment concepts of treatment holidays and different treatment intervals beyond 4 weeks have been proposed. Up to now, there are no data available on immunology and natalizumab concentration in blood and CSF. Design/Methods: Patients were analyzed during cessation of natalizumab and at different infusion intervals of natalizumab (every 4, 5 or 8 weeks) using FACS analysis of blood and CSF at different timepoints. In addition, free and cell-bound quantities of natalizumab were measured. Results: After cessation of natalizumab plasma concentrations decreased by 54% in month 1, 90% in month 2 and 99,7% in month 3 and 4. We could observe cell-bound natalizumab in blood 2 up to 4 months after stop of treatment. Blood and CSF analysis in patients with relapses after cessation of natalizumab demonstrated no cell-bound natalizumab and plasma concentrations which were decreased to 99% from baseline levels. We could demonstrate different pre infusion plasma concentrations of natalizumab for treatment intervals of 4 (25±5 µg/ml), 5 (15±5 µg/ml) or 8 weeks (6±5µg/ml). Post infusion natalizumab levels ranged from 60µg/ml up to 130µg/ml independent of the respective treatment interval. Regarding pre-infusion cell-bound natalizumab, we could describe MFI of 3500-6000 for 4 weeks interval, 1000-2500 for 5 and 1000-1200 for 8 weeks treatment interval. Conclusions: Monitoring pharmakokinetics and –dynamics can be helpful in analysis of treatment holidays and different application intervals of natalizumab. Supported by: Biogen Idec. Disclosure: Dr. Hainke has nothing to disclose. Dr. Ziemssen has received personal compensation for activities with Biogen Idec, Bayer Healthcare, Novartis, Sanofi-Aventis Pharmaceuticals, Inc., Teva Neuroscience, and Synthon. Dr. Ziemssen has received research support for from Bayer Healthcare, Biogen Idec, Novartis, Teva Neuroscience, and Sanofi-Aventis Pharmaceuticals, Inc. Dr. Sehr has nothing to disclose. Dr. Thomas has received research support from Teva Neuroscience. Dr. Schultheiss has nothing to disclose.