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.