Switching from Natalizumab to Fingolimod

People taking natalizumab often have to stop and switch to something else, such as if you are JC virus positive and have been on previous immunosuppression.

You don’t want to immunosuppress in case the person has sub clinical PML. You don’t want to wait too long because disease will reactivate.

What happens if the time interval is only a month between stopping and starting?

Naegelin Y, Rasenack M, Andelova M, Von Felten S, Fischer-Barnicol B, Amann M, Mehling M, Kappos L, Sprenger T, Derfuss T. Shortening the washout to 4 weeks when switching from natalizumab to fingolimod and risk of disease reactivation in multiple sclerosis. Mult Scler Relat Disord. 2018 Jul 6;25:14-20. doi: 10.1016/j.msard.2018.07.005. [Epub ahead of print]


There is limited evidence about the optimal length of washout when switching from natalizumab to fingolimod.


To study if a washout period of 4 weeks is associated with less disease activity compared to 8 weeks.


25 patients with Relapsing Remitting Multiple Sclerosis were included in an open label, prospective study with a follow-up of 108 weeks. The primary endpoint (PE) was defined as “time to first relapse or MRI disease activity up to week 56”. In addition, a recurrent event analysis (REA) was performed up to week 108.


The PE was not met (HR 0.67, 95% CI [0.22,1.97], p = 0.462). Number of relapses before stopping natalizumab was positively associated with the hazard of relapse (HR 3.91, p = 0.0117, 95% CI [1.36, 11.28]). The REA showed a reduction of the hazard to develop a relapse by 77% (HR 0.23, 95% CI [0.08, 0.69], p = 0.00854) in favour of the cohort with 4 weeks washout.


Our study suggests that switching from natalizumab to fingolimod with a shorter washout of 4 weeks might reduce the risk of disease reactivation after switching.

As you get natalizumab every 4 weeks you will maintain immunosuppression for that long, but obviously if PML is sub clinical, the risk of it developing clinically is going to be there.

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  • MD, what is the mean treatment duration on natalizumab and what are the causes for discontinuation?

    Also, the PML numbers on natalizumab are stuck on December last year. Any update?

  • Thanks for article,

    As someone taking Natalizumab, I am always keen to read about updates and gain a better take on options if one day my JC level changes.

    I have read about extended dosing, and understand some clinics now regularly prescribe 6 week infusion cycles and I’ve even heard of up to 8 mentioned.

    I understood, that there have been positive data from Scotland that this dosing puts patience at no greater risk of relapse. Therefore, does this imply that the suppression is longer than 4 weeks?

    Anyway, good to know that fingo is an option. I for some reason thought it wasn’t after turning JC +. Always learning.

    I know there are past articles about switching from nat to other medications. But wondered if a new post could be provided on this.

    I think many of us taking the drug, are keen to understand things such as PML risk, post nat options (are there drugs are ruled out if you turn JC+?), switching protocols etc,
    perhaps could be added to capture these and updated bi annually? Just a thought, I know you guys have limited time.

    Keep up the good work

  • Well over 4 years and running no one on Tysabri extending time between doses has ever contracted PML. Any neuro not discussing dose extension of 5, 6, 7, or 8 weeks with Tysabri patients is being grossly negligent, IMO.

    My wife switched from Tysabri to Ocrevus over a year ago and it was the biggest mistake in treatment we have ever made. She went from living a life free from MS (2006 – 2017) to a resumption of fatigue and multiple MS symptoms. Not to mention a probable increased cancer risk (IMHO).

    I believe there is a real need to halt the exodus from Tysabri only because of being JCV positive. Neuros need to get their shit together and do what is best for their JCV+ Tysabri patients rather than switching to less effective DMTs, including Gilenya. I hope Tysabri patients having good success are horrified at the prospect of switching. I can only wish we had been.

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