Overdosing with Natalizumab

van Kempen ZL, Leurs CE, Witte BI, de Vries A, Wattjes MP, Rispens T, Killestein J. The majority of natalizumab-treated MS patients have high natalizumab concentrations at time of re-dosing.
Mult Scler. 2017 May 1:1352458517708464.

BACKGROUND:Natalizumab is efficacious in the treatment of relapsing-remitting multiple sclerosis. All patients receive the same treatment regimen of 300 mg every 4 weeks, despite differences in pharmacokinetics between individual patients.
OBJECTIVE:To give neurologists insight into natalizumab concentrations at time of re-dosing, we investigated longitudinal natalizumab concentrations in 80 patients in relation to disease activity, with possible influencing factors.
METHODS: In a prospective observational cohort study, natalizumab trough serum concentrations were measured in 80 patients. Data on demographics, duration of treatment, Expanded Disability Status Scale, clinical exacerbations, brain magnetic resonance imaging (MRI), and body weight were collected.
RESULTS: We measured high (≥10 µg/mL) natalizumab trough concentrations in 94% of patients. Intra-individual concentrations were stable. The spread in concentrations was substantial and did not correlate with disease activity.
INTERPRETATION: The majority of patients showed high natalizumab serum concentrations at time of re-dosing. Alternative treatment regimens could lead to more efficient use of natalizumab, but caution is warranted regarding the possibility of recurrence of disease activity. Prospective clinical trials are needed to establish the safety of extended dose intervals in natalizumab treatment.

Some people taking natalizumab report the feeling that it is wearing off, about a week before their next infusion. This current study rather suggests the opposite. This indicates that you don’t need as much natalizumab. This study looks at the circulating levels of natalizumab and finds that by the time the next infusion comes along, there is still large amounts of natalizumab within the blood. This suggests that the next infusion is too early. However, be warned when you play with natalizumab. If the concentration of natalizumab wears off and C49Ddis no longer blocked then the cells are ready binding to CD016/VCAM-1 and stream into the brain to cause a rebound attack.  However, reducing the frequency of dosing should reduce costs and time spent under a “drip” Is it in the companies interest to sell less drug?

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  • My MS nurse had told me that natalizumab's halflife is 11 days. That means that if the concentration follows the exponential decay, when the next infusion is due (after 28 days), then our bodies still have 17% of the natalizumab infused last time.
    If natalizumab was given every 6 weeks, then we would have 7% of last infusion. Do you think then it would be more reasonable to administer it every 6 instead of 4 weeks?

    • We have seen evidence that delayed infusion works but how often does it need to injected.

      How often do you need to inject copaxone…Daily wheres the evidence, now three times a week, wheres the evidence it cant be one a week?

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