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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  MSMT s 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 .

Treatment of natalizumab‐associated PML with filgrastim