An Observational Study to Evaluate Disease Control, Safety and Immunological Changes in Patients With Relapsing Remitting Multiple Sclerosis (RRMS) Transferred From Previous Treatment With Natalizumab to Fingolimod.

The risk of progressive multifocal leukoencephalopathy (PML) upon treatment with natalizumab increases over time, at least into the 3rd year of therapy. Many Multiple Sclerosis (MS) patients who are currently being treated with natalizumab, as well as their physicians, are looking for alternative MS treatments, fingolimod being one. In transferring patients from natalizumab to fingolimod, it is not known if their co-administration leads to an increased risk of adverse effects due to a shared feature that both have immunomodulation as a mechanism of action. Therefore a sufficient washout period after natalizumab discontinuation and fingolimod initiation is desirable. However, this has to be balanced with the increasing risk over time of recurring disease activity while patients are untreated.

This study prospectively evaluates how safe it is to switch patients from natalizumab to fingolimod treatment following cessation of natalizumab treatment, in a cohort of RRMS patients.

Safety of the proposed transition paradigms is defined as both traditional safety measures but also recurrence of disease activity during a washout period of 8 weeks after the cessation of natalizumab treatment followed by fingolimod treatment initiation. An interim analysis of the first 15 patients revealed a clinical and MRI activity in 38.5 and 64.3% respectively. Therefore a shorter interval was defined for any subject entering into this study after october 2013: the interval was defined to be 4 weeks for those patients.

Overall, the study aims to provide guidance to physicians on the management of natalizumab-treated patients for whom a transition to fingolimod treatment is considered an appropriate treatment alternative.

An evidence based rationale for changing to a 4 or 8 week wash out period is not possible due to missing evidence. Due to the known risk of PML for patients being treated with natalizumab for more than 2 years, starting fingolimod during natalizumab therapy seems to be inappropriate, as an elevated risk for JC Virus (JCV) manifestation could be expected in this constellation. On the other hand considerable shortening of the 8-weeks interval could be favorable to prevent clinical and MRI activity. An interval of 4 weeks between last dose of natalizumab and first dose of fingolimod seemed to be an appropriate compromise to balance risks and benefits of this treatment transition.