Abstract Details

Title Effects of Long-Term Natalizumab Treatment on Cell Bound Natalizumab and Very Late Antigen-4 Expression

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 190

Objective

Background BACKGROUND: NAT is a disease-modifying treatment for multiple sclerosis (MS) patients. The humanized monoclonal antibody inhibits the transmigration of T- and B-cells throughout the blood brain barrier by blocking the VLA-4 on leukocytes. Until now there are no data available about the influence of long-term NAT treatment on cell bound NAT and VLA-4 expression of immune cells.

Design/Methods DESIGN/METHODS: 10 RRMS patients were analyzed at baseline and at month 1, 2, 3, 6, 9, 12, 24 and 36 after starting NAT treatment. Blood samples were obtained before the 4-weekly intravenous infusion of 300mg NAT. After isolating PBMC from heparinized blood, cells were stained with several fluorescence labeled antibodies containing anti-VLA4 and anti-NAT antibodies for measurement of cell bound NAT and VLA-4 expression by FACS. Additionally free NAT serum concentration was determined by using a HL60-cell-assay.

Results RESULTS: After starting NAT treatment VLA-4 expression of blood CD3+T-cells decreases to 51±6% compared to baseline. We saw an increase of cell bound NAT on blood CD3+T-cells to MFI values of 2891±543 after first NAT infusion (baseline: 1393±283). Both VLA-4 expression and MFI values of cell bound NAT remained individually stable for period of analysis, while showing a big inter-individual-variability. We measured free NAT serum concentrations of 28,55±2,7 pre and 99,6± ,1 post infusion for patients with an average treatment duration of 27 months. Determination of free NAT serum concentration one year later showed comparable values.

Conclusions CONCLUSIONS: Long-term NAT therapy causes a stable amount of free and cell bound NAT as a constant decrease of the VLA-4 expression of immune cells. All of them could be potential dosing tools as well as monitoring parameters for effectiveness and safety of this drug therapy.

Authors/Disclosures
Undine Hainke (Lenkr of Clinical Neuroscience) PRESENTER	No disclosure on file
Jerry S. Wolinsky, MD, FAAN (McGovern Medical School, UTHealth)	Dr. Wolinsky has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avotres. Dr. Wolinsky has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Brainstorm Cell Therapeutics. Dr. Wolinsky has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cleveland Clinic Foundation. Dr. Wolinsky has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Wolinsky has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Inmagene. Dr. Wolinsky has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis/Sandoz. Dr. Wolinsky has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Wolinsky has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. Dr. Wolinsky has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for University of Alabama Birmingham. Dr. Wolinsky has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Wolinsky has received intellectual property interests from a discovery or technology relating to health care. Dr. Wolinsky has received intellectual property interests from a discovery or technology relating to health care.
Tony Sehr	No disclosure on file
	No disclosure on file
Katja Thomas, MD (Centre of Clinical Neuroscience, Neurological University Clinic)	No disclosure on file
Tjalf Ziemssen, MD, FAAN (University Clinic Dresden)	Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS . Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Roche. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sanofi. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for TEVA. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for Dresden Internation University. The institution of Dr. Ziemssen has received research support from Novartis. The institution of Dr. Ziemssen has received research support from Merck. The institution of Dr. Ziemssen has received research support from Sanofi. The institution of Dr. Ziemssen has received research support from BMS. The institution of Dr. Ziemssen has received research support from Roche.

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