Objective:

To determine if CD49d receptor occupancy remains stable over time in patients that change from IV-NTZ to SC-NTZ either every four or six weeks. 

Background:

Natalizumab (Tysabri®) is a humanized monoclonal antibody that selectively binds the α4-integrin (CD49d), preventing the migration into the central nervous system (CNS). It is indicated for the treatment of Relapsing Remitting Multiple Sclerosis (RRMS). However, its use is associated with a blockade of immunosurveillance in the CNS. For this reason, immunomonitoring of Natalizumab (NTZ)-treated patients is required.

Design/Methods:

Longitudinal study of patients treated with IV-NTZ at least during 6 doses changing to SC-NTZ while maintaining the same therapeutic regimen as before. Peripheral blood samples were analysed through quantitative flow cytometry to determine CD49d receptor occupancy in CD4⁺, CD8⁺ and CD19⁺ lymphocytes. Each patient received 6 consecutive SC-NTZ doses either every 4 or 6 weeks and the samples were analysed at 3 time points (before first, third, and seventh dose).

Results:

A total of 17 RRMS patients received Tysabri. Patients were treated every 6 wk (n=13) or every 4wk (n=4). From the 13 patients treated every 6wk, after the change from IV to SC administration, surface expression of CD49d and bound NTZ molecules remained stable over time. The mean % of CD49d receptor occupancy was 67 ± 11.27% in CD4⁺ T lymphocytes, 58 ± 12.19% in CD8⁺ T lymphocytes and 58 ± 12.61 % in CD19⁺ B lymphocytes, and remained stable. In patients treated every 4wk, these parameters also remained stable over time, with receptor occupancy percentages of 81 ± 6.65%, 71 ± 7.65% and 70 ± 8.85%, respectively. No changes in disease activity were observed.

Conclusions:

Our clinical practice results show that CD49d receptor occupancy remains stable over time in patients who have switched from IV-NTZ to SC-NTZ administration, either every 4 or 6 weeks.