Treatment of natalizumab‐associated PML with filgrastim

OBJECTIVE: There is no consensus on the treatment of progressive multifocal leukoencephalopathy (PML) occurring in multiple sclerosis (MS) patients treated with natalizumab (Nz). We report novel immune activating treatment with filgrastim of Nz‐associated PML in MS patients treated at Rush University Medical Center. METHODS: We retrospectively analyzed 17 Nz‐PML patients treated at this single tertiary referral center between 2010 and 2017. We reviewed the clinical symptoms, diagnostic methods, survival, outcome and MS modifying therapy (MSMT) after Nz‐PML. RESULTS: PML occurred after an average of 49 Nz infusions. To facilitate JCV elimination by accelerating immune reconstitution inflammatory syndrome (IRIS), all patients received subcutaneous filgrastim upon PML diagnosis and discontinuation of Nz; eight received plasma exchange (PLEX). Earlier than previously published, PML‐IRIS occurred in 15 of 17 (88.2%) patients within a mean of 57.4 days (SD 21.20) after the last Nz infusion. Seven patients recovered to or near baseline. There were no PML/IRIS–related fatalities but one patient committed suicide 2.5 years later. PLEX had no impact on PML outcome. Of 17 patients, 3 (18%) had MS relapses within 1 year after PML, and 5 (29%) beyond 1 year of PML onset, which is lower than expected in highly active MS patients. Eight patients started MSMTs after Nz‐PML on an average of 26 months after Nz withdrawal. INTERPRETATION: Our findings indicate that immunoactivation with filgrastim during PML and careful management of subsequent IRIS is likely beneficial in patients with Nz‐PML, without worsening MS. The clinical course of MS may be ameliorated by PML.