Saturday, 30 April 2016

ClinicSpeak & NeuroSpeak: sequencing DMTs switching from natalizumab to alemtuzumab

Can you switch from natalizumab to alemtuzumab safely? #ClinicSpeak #Neurospeak #MSBlog

"Finally, our algorithm for switching patients at high-risk of PML to other DMTs, in particular alemtuzumab, is in print. We originally published this algorithm on the blog way back in 2014 so why publish it in a journal now? Firstly, it is always good practice to get your work peer-reviewed and secondly it is not accepted practice to quote a blog."

"It is ironic that the day after the EMA announces a positive opinion on daclizumab as a treatment for relapsing forms of MS our paper comes out in print. Ironic in that I have being making the case for daclizumab being the agent of choice post-natalizumab. This means our recommendations will be out of date very soon. In anticipation of this I have already updated the recommendations by including both daclizumab and rituximab as potential switch agents. The daclizumab recommendation is based on scientific principles. Let's hope Biogen and Abbvie do a switch study to produce the necessary data to support this recommendation. In comparison the rituximab recommendation is based on real-life data from Sweden. Despite the latter, NHS England have already said no to rituximab off-label. However, the fact that we can't use rituximab in the NHS in England and Wales doesn't mean other neurologists reading this blog can't. So may be the blog is the best platform for keeping up-to-date with our thinking on this issue?"

Figure: adapted from Giovannoni et al. 

Giovannoni et al. Neurological dilemmas: Switching patients at high risk of PML from natalizumab to another disease-modifying therapy. Pract Neurol doi:10.1136/practneurol-2015-001355

There are several options for switching people with multiple sclerosis (MS) who are at high risk of developing progressive multifocal leukoencephalopathy (PML) from natalizumab to alemtuzumab. However, some of these have risks that need to be managed, for example, the risks of carrying over asymptomatic PML from natalizumab on to the new therapy, and the risk of rebound disease activity associated with a prolonged washout after starting natalizumab. We propose a pragmatic bridging strategy, using another disease-modifying therapy (DMT), to reduce the risk of switching from natalizumab to alemtuzumab. We also discuss the caveats and subtleties associated with sequencing DMTs in MS and the complex decision making involved.

CoI: multiple

9 comments:

  1. I visited the Practical Neurology website. I am curious about why you did not pay the fee to publish the article as open access. Your institution might have an open access fund for researchers who publish. Even if the article is not open access, you have the right to place "the final accepted manuscript (but not the final published version)" in your institutional repository. Will you do so and provide us the link? This will permit anyone interested to read the work in full. Thank you. Liz Levey

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    Replies
    1. Paying for open access it is £1,000-£3000 to publish open access. If you have no funds for this it is a drain on resources.

      Our Institution does have an instituitional repository and from April the University wants every thing to go into this repository so it can go in for the next research assessment as it has to be open access 3 months from acceptence. This bonkers because many journals take longer than 3 months to publish even online and thereofre the contents have to go live before the actual paper is published...bonkers.

      Maybe ProfG has done this

      Delete
    2. I'm sure if you email one of the authors will be happy to send you a personal copy; mine is k.schmierer@qmul.ac.uk.

      Delete
    3. Liz says
      Many thanks for your reply. The policy does sound peculiar. Does this mean that you won't be able to mount your paper in the Repository?

      A workaround might be to mount it in academia.edu, which is what a lot of researchers do. About paying for open access, most donors will cover those costs if you do any research with donor funding.

      Delete
    4. It can be mounted in a repository.

      However you are not correct that all funders pay for open access. In the uK the MS Society say they want their papers open access but will not pay for the publication.

      Delete
  2. Why is the period on the bridging agent so much shorter when switching from natazlizumab to cladribine because of high PML risk? I was advised that a period of less than two months on fingolimod is long enough.

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  3. Based on the Swedish data you cited and further evidence available on the efficacy of Rituximab in MS why would one consider Rituximab as a bridging agent rather than a permanent switching option in the same high efficacy category as Alemtuzumab?

    Also wondering whether you have considered the possible higher risk of other serious (fatal) infections while bridging from Rituximab to Alemtuzumab as seen in patients with chronic lymphocytic leukaemia http://m.jco.ascopubs.org/content/28/29/4500.short
    (granted the doses were much higher in this study and patients had also received fludarabine but it is a safety signal one should bear in mind)

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  4. The best option is to take Natalizumab out if the equation (the patient should have never started on it in the first place). Case solved.

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    Replies
    1. Yes, I think Barts would be doing a great service if they started phasing out the prescription of Tysabri altogether. 600+ deaths. Alemtuzumab is much safer for all of its problems and the new stuff looks better as well.

      Delete

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