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Mild progressive multifocal leukoencephalopathy after switching from natalizumab to ocrelizumab

Alyssa A Toorop1, Zoë Y G van Lierop2, Eva E M Strijbis2

  • 1From the Department of Neurology (A.A.T., Z.Y.G.L., E.E.M.S., B.A.J., Z.L.E.K., J.K.), Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, MS Center Amsterdam; Department of Clinical Chemistry (C.E.T.), Neurochemistry Laboratory and Biobank, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam; Department of Ophthalmology (A.P.), Neuro-ophthalmology Expertise Center, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Department of Diagnostic and Interventional Neuroradiology (M.P.W.), Hanover Medical School, Hanover, Germany; Department of Radiology and Nuclear Medicine (M.P.W., F.B.), Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, MS Center Amsterdam, the Netherlands; Department of Neuroinflammation (F.B.), Queen Square MS Centre, UCL Institute of Neurology, Faculty of Brain Sciences, University College London; and National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (F.B.), London, United Kingdom. a.toorop@amsterdamumc.nl.

Neurology(R) Neuroimmunology & Neuroinflammation
|October 14, 2020
PubMed
Abstract

Insights

Switching natalizumab to ocrelizumab in multiple sclerosis (MS) patients with progressive multifocal leukoencephalopathy (PML) resulted in mild PML-immune reconstitution inflammatory syndrome (IRIS). B-cell depletion did not appear to worsen PML-IRIS in these cases.

Area of Science:

  • Neuroimmunology
  • Neurology
  • Infectious Diseases

Background:

  • Progressive multifocal leukoencephalopathy (PML) is a rare, opportunistic infection of the central nervous system.
  • Natalizumab is associated with an increased risk of PML.
  • Switching to B-cell depleting therapies like ocrelizumab is a strategy considered in MS patients with PML.

Observation:

  • Two cases of relapsing-remitting multiple sclerosis (MS) patients who developed PML after natalizumab discontinuation and subsequent ocrelizumab initiation.
  • Patients experienced mild immune reconstitution inflammatory syndrome (IRIS) despite B-cell depletion.
  • Serum neurofilament light (NfL) levels increased during PML-IRIS.

Findings:

  • Carryover PML after natalizumab to ocrelizumab switch presented with mild IRIS.
  • Ocrelizumab-induced B-cell depletion did not seem to exacerbate PML-IRIS in these patients.
  • Treatment with mefloquine, mirtazapine, and methylprednisolone stabilized PML-IRIS lesions.

Implications:

  • B-cell depletion may not necessarily worsen PML-IRIS in MS patients.
  • This suggests a potentially safer transition strategy for MS patients with PML.
  • Further research is needed to confirm the safety and efficacy of ocrelizumab in this context.

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