Article

Switching therapy from natalizumab to fingolimod in relapsing-remitting multiple sclerosis: Clinical and magnetic resonance imaging findings

Multiple Sclerosis Centre of Padova, University Hospital, Italy.
Multiple Sclerosis (Impact Factor: 4.86). 11/2012; 18(11):1640-3. DOI: 10.1177/1352458512464282
Source: PubMed

ABSTRACT Clinical and/or neuroimaging evidence of disease reactivation has been described in multiple sclerosis (MS) patients after a break from natalizumab. Whether fingolimod might be a therapeutic option following natalizumab needs to be evaluated. Twenty-two relapsing remitting MS patients having JC virus antibodies (JCVAb+) in serum were shifted from natalizumab to fingolimod after a three-month washout period. Neurological evaluation with the Expanded Disability Status Scale (EDSS) was performed monthly for a mean follow-up period of nine months. In 20/22 patients, brain magnetic resonance imaging (MRI) was obtained within one month after therapy initiation. Disease reactivation was observed in 11/22 (50%) patients: clinical relapses in six patients (four patients within the first month of therapy) and MRI activity in a further five patients (three patients within the first month of therapy). Clinical and/or MRI signs suggestive of disease rebound were observed in three patients. Our data indicate that fingolimod does not exert clinical activity quickly enough to stop MS reactivation after a break from natalizumab.

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    • "It is interesting to note that, 21 months after her last natalizumab infusion, the patient has not developed any clinical or MRI findings suggesting re-appearance of MS activity. This is in contrast to several reports showing reactivation of MS within 15 months after the cessation of natalizumab treatment in 50% or more of cases [8] [9]. "
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    ABSTRACT: A multiple sclerosis (MS) patient developed progressive multifocal leukoencephalopathy (PML) after 43months of natalizumab treatment. New clinical and magnetic resonance imaging (MRI) findings were initially misinterpreted as breakthrough MS disease activity and natalizumab treatment was replaced by rituximab treatment. The patient had a single infusion of rituximab 1000mg before a definite PML diagnosis was confirmed. Despite undetectable levels of B-cells, JC virus DNA became undetectable in the cerebrospinal fluid by quantitative polymerase chain reaction. The patient partially recovered without any clinical or MRI signs of new MS activity. These findings suggest that B-cell depletion in a non-immune compromised individual did not prevent the patient from clearing the JC virus infection. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of the neurological sciences 04/2015; 353(1-2). DOI:10.1016/j.jns.2015.04.010 · 2.26 Impact Factor
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    • "Studies have demonstrated that switching to glatiramer acetate is better than switching to no therapy, but still gives less than ideal disease control [24]. Studies of switching from natalizumab to fingolimod have shown mixed results [25] [26] [27], but anecdotally the majority of patients do well with this change. One specific issue regarding the discontinuation of natalizumab, particularly as this is often done in the setting of a positive JC virus antibody test, is the emergence of immune reconstitution inflammatory syndrome (IRIS – see below) after 4–12 weeks (often after a new therapy has commenced) [28] [29]. "
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    ABSTRACT: Natalizumab treatment has been shown to be very efficacious in clinical trials and very effective in clinical practice in patients with relapsing-remitting multiple sclerosis, by reducing relapses, slowing disease progression, and improving magnetic resonance imaging patterns. However, the drug has also been associated with a risk of progressive multifocal leukoencephalopathy (PML). The first consensus statement on natalizumab use, published in 2011, has been updated to include new data on diagnostic procedures, monitoring for patients undergoing treatment, PML management, and other topics of interest including the management of patients discontinuing natalizumab.
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