Switching therapy from natalizumab to fingolimod in relapsing-remitting multiple sclerosis: Clinical and magnetic resonance imaging findings
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.
- SourceAvailable from: Jan Lycke
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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  . "
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 . Studies of switching from natalizumab to fingolimod have shown mixed results   , 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)  . "
ABSTRACT: In this third and final part of our review of multiple sclerosis (MS) treatment we look at the practical day-to-day management issues that are likely to influence individual treatment decisions. Whilst efficacy is clearly of considerable importance, tolerability and the potential for adverse effects often play a significant role in informing individual patient decisions. Here we review the issues surrounding switching between therapies, and the evidence to assist guiding the choice of therapy to change to and when to change. We review the current level of evidence with regards to the management of women in their child-bearing years with regards to recommendations about treatment during pregnancy and whilst breast feeding. We provide a summary of recommended pre- and post-treatment monitoring for the available therapies and review the evidence with regards to the value of testing for antibodies which are known to be neutralising for some therapies. We review the occurrence of adverse events, both the more common and troublesome effects and those that are less common but have potentially much more serious outcomes. Ways of mitigating these risks and managing the more troublesome adverse effects are also reviewed. Finally, we make specific recommendations with regards to the treatment of MS. It is an exciting time in the world of MS neurology and the prospects for further advances in coming years are high.Journal of Clinical Neuroscience 06/2014; DOI:10.1016/j.jocn.2014.01.017 · 1.32 Impact Factor
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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.Neurologia 11/2011; 27(7):432-41. DOI:10.1016/j.nrl.2011.09.008 · 1.35 Impact Factor