Disease reactivation after cessation of natalizumab and switching to fingolimod

Rinaldi et al. Switching therapy from natalizumab to fingolimod in relapsing-remitting multiple sclerosis: clinical and magnetic resonance imaging findings. Mult Scler. 2012;18:1640-3.

Background: Clinical and/or neuroimaging evidence of disease reactivation has been described in MSers  after a break from natalizumab. 

Objective: To evaluate fingolimod as therapeutic option following natalizumab. 

Methods: Twenty-two relapsing remitting MSers having JC virus antibodies (JCVAb+) in serum were switched 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. 

Results: In 20/22 MSers, MRI was obtained within one month after therapy initiation. Disease reactivation was observed in 11/22 (50%) MSers: clinical relapses in six MSers (four MSers within the first month of therapy) and MRI activity in a further five MSers (three MSers within the first month of therapy). Clinical and/or MRI signs suggestive of disease rebound were observed in three MSers. 

Conclusions: Our data indicate that fingolimod does not exert clinical activity quickly enough to stop MS reactivation after a break from natalizumab.

Rigau et al. Lethal multiple sclerosis relapse after natalizumab withdrawal. Neurology. 2012 Oct 24. [Epub ahead of print]

Jander et al. Emerging tumefactive multiple sclerosis after switching therapy from natalizumab to fingolimod. Mult Scler. 2012;18:1650-2. doi: 10.1177/1352458512463768.
"These studies and case reports confirm mine and many other neurologists' observations of rebound on natalizumab withdrawal. Most of us feel that this rebound is in excess of what activity MSers had before they started natalizumab. How to prevent it? It is difficult, because you want to make sure that JCV+ MSers who are switching from natalizumab (Tysabri) to fingolimod (Gilenya) are not in the pre-symptomatic phase of PML, which is why we advocate a 3 month washout period. The washout allows your own immune system to reconstitute the CNS and find any rogue virus. The problem with this strategy is that it allows your MS to comeback with a vengeance. Some of us have started prescribing pulsed monthly steroids to cover this period, but this does not appear to prevent the rebound entirely. There are several trials testing different washout periods and switching options that will hopefully allow us to make more evidence-based recommendations shortly. At present I am too concerned about carry-over PML on fingolimod to recommend anything less than a 3 month washout. If we can increase the diagnostic confidence of excluding early asymptomatic PML I will obviously change my recommendation. Please stay tuned to this blog; we will come back to you with more posts as data becomes available."

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