Monday, 31 December 2012

Research: fingolimod after natalizumab keeps relapses at bay

#MSBlog: How soon after stopping natalizumab (Tysabri) do you start fingolimod (Gilenya)?

Epub: Havla et al. Fingolimod reduces recurrence of disease activity after natalizumab withdrawal in multiple sclerosis. J Neurol. 2012.

Background: After discontinuation of natalizumab (Nz), MS disease activity often recurs. 


"The level of rebound activity can be very severe!"

Objective: This study assessed the recurrence of clinical disease activity during the first year after switching from Nz to fingolimod (Fingo) in RRMSers. 

Methods: The number of relapses and the annualized relapse rate (ARR) before, during and after Nz discontinuation were determined and compared between 26 MSers who switched to Fingo within 24 weeks, and 10 MSers who remained without disease modifying therapy (therapy free group = TFG). 

Results: Median follow-up post-Nz discontinuation was 55.1 weeks. In a subgroup (n = 20), the occurrence of contrast-enhancing-lesions (Gd+) on magnetic resonance imaging (MRI) was determined. Eleven MSers (42 %) in the Fingo group and seven MSers (70 %) in the TFG had one or more relapses after cessation of Nz during follow-up (p < 0.05). One of the 11 (9 %) MSers in the Fingo group and 6/9 (67 %) MSers in the TFG showed Gd+ lesions during follow-up (p < 0.05). MSers who switched to Fingo  ≤ 12 weeks after Nz discontinuation (n = 9) showed a trend for a lower post-Nz ARR compared to MSers who started Fingo therapy >12 weeks after Nz was stopped (n = 17). Most relapses in the Fingo group occurred just before or within 8 weeks after starting Fingo. 

Conclusion: These observation suggests that initiation of Fingo treatment after Nz discontinuation reduces the recurrence of disease activity compared to withdrawal without further immunomodulatory treatment. In the Fingo group the ARR tended to depend on the time interval between discontinuation of Nz and initiation of Fingo.

"These results support our recent change in practice to limit the washout period when switching from Nz to Fingo. The sooner you switch the greater the likelihood of preventing post-Nz rebound!"


Other related posts of interest:

01 Dec 2012
"The potential rebound in MS disease activity that is commonly seen after withdrawal of natalizumab, and now fingolimod, reminds me of the book 'Waiting for the Barbarians' by JM Coetzee, which I read as a teenager.

27 Jul 2012
Rebound in MS disease activity on fingolimod withdrawal. Epub: Hakiki et al. Withdrawal of fingolimod treatment for relapsing-remitting multiple sclerosis: report of six cases. Mult Scler. 2012 Jul. The objective of this study is to ...

19 Feb 2012
Rebound of disease activity after withdrawal of fingolimod (FTY720) treatment. Arch Neurol. 2012;69:262-4. BACKGROUND: The oral sphingosine-1-phosphate receptor modulator fingolimod (FTY720/Gilenya) was recently ...

03 Jul 2012
BACKGROUND AND PURPOSE: MSers discontinuing natalizumab are at risk of rebound of disease activity. METHODS: In the present multi-center, open-label, non-randomized, prospective, pilot study, the investigators' ...

31 Oct 2012
Natalizumab dramatically reduces relapses in MSers with active MS, but it may induce progressive multifocal leukoencephalopathy (PML).(1) A rebound of MS or an immune reconstitution inflammatory syndrome (IRIS) were ...

30 Oct 2012
Clinical and/or MRI signs suggestive of disease rebound were observed in three MSers. ... "These studies and case reports confirm mine and many other neurologists' observations of rebound on natalizumab withdrawal.

CoI: multiple

1 comment:

  1. good news
    it's been interesting watching the evolution of Tysabri (on the market, pulled off the market, back on) and the development of techniques for dealing with PML (testing for JC virus, how to manage IRIS). And now perhaps a better way to manage the discontinuation of Tysabri.
    Much effort being made to reduce the risk seen with Tysabri.

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