Fingolimod To Treat Severe Multiple Sclerosis After Natalizumab-Associated Progressive Multifocal Leukoencephalopathy: A Valid Option? (P2.250)

OBJECTIVE : We report two cases of multiple sclerosis patients who, after natalizumab-associated progressive multifocal leukoencephalopathy and several relapses on immunomodulatory treatment, have been treated with fingolimod, without any multiple sclerosis relapse nor progressive multifocal leukoencephalopathy worsening. BACKGROUND : Natalizumab (NZ) is a humanized recombinant monoclonal antibody, which prevents leukocyte infiltration into Central Nervous System and is used as a treatment for active relapsing remitting (RR) multiple sclerosis (MS). However since 2006, progressive multifocal leukoencephalopathy (PML) has been reported as a serious adverse event of NZ. It is caused by JC virus reactivation, and is usually observed in prolonged and severe immunosuppression. Treatment of NZ-associated PML consists in NZ discontinuation, but NZ cessation has been associated with reactivation of MS: it may be responsible for additional worsening of the neurological status. No treatment has been proved efficient for rebound prevention. Fingolimod, an oral sphingosine-1-phosphate-receptor modulator, prevents relapses in RR MS, and has been recently proposed as an alternative treatment after NZ cessation motivated by PML risk. However, no treatment has been proposed after MS reactivation secondary to NZ interruption due to PML. DESIGN/METHODS These two women were followed in our department for severe RR MS. After failure of different immunomodulatory and immuosuppressant treatments, NZ was introduced. After 40 infusions for both patients, cognitive disorders revealed PML, then NZ was interrupted. Severe MS relapses occurred between 4 and 5 months after NZ discontinuation. After failure of immunomodulatory treatment, both patients were treated with fingolimod. RESULTS The outcome was successful on clinical and MRI disease activity, without clinical or radiological worsening of the progressive multifocal leukoencephalopathy. CONCLUSIONS Using fingolimod for severe multiple sclerosis after natalizumab-associated progressive multifocal leukoencephalopathy may be an option, under close clinical and radiological monitoring.