BACKGROUND:In natalizumab-treated relapsing-remitting MS (RRMS) patients, various extended interval dosing strategies are under evaluation to minimize severe treatment-associated side effects, mainly progressive multifocal leukoencephalopathy development. Up to now, it has not been presented any approach, even in form of assay design, to determine the optimal percentage of CD49d receptor occupancy (RO) associated with a favorable clinical, radiological, and immunological response.
METHODS:A multiparametric quantitative flow cytometry (QFCM) method was settled to measure CD49d RO on peripheral blood lymphocytes. The analytical protocol was tested in a 6-month follow-up from 19 RRMS patients treated with the natalizumab standard dosing of every 4 weeks or an extended-interval dosing of every 6 weeks.
RESULTS: Extended natalizumab dose schedule promoted an increase of CD49d molecules per cell surface and a reduction of CD49d RO levels. The reduction observed on CD49d RO was not only depending on dose schedule but also on individual parameters such as body mass. Interestingly, individual clinical outcome was apparently the same between the different dose schedules or even better with the extended interval dosing.
CONCLUSIONS: Following up CD49d RO levels with a well-regulated monitoring work scheme is crucial to further identify over-/under-treated patients and to define a safe, personalized natalizumab regimen
Natalizumab has one of the clearesst mechanisms of all the MS drugs. It works by binding to CD49d or very late antigen 4 or alpha 4 integrin (same thing different names) to block it binding to vascular cell adhession molecule. This gets up regulated at sites of inflammation and is use by white blood cells (T cells, Bcells and monocytes) to get into the inflammaed brain. Block this and they can’t get in.