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Presentation and Outcome in S1P-RM and Natalizumab-Associated Progressive Multifocal Leukoencephalopathy: A

Julie C Blant1, Nicola N De Rossi1, Ralf Gold1

  • 1From the Service of Neurology (J.C.B., R.A.D.P., R.B.-V.), Department of Clinical Neurosciences, Lausanne University Hospital (Centre Hospitalier Universitaire Vaudois) and University of Lausanne, Switzerland; Regional Multiple Sclerosis Center (N.N.D.R.), ASST-Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology St. Josef-Hospital (R.G., I.A.), Ruhr University Bochum, Germany; Centre Hospitalier Régional Universitaire de Tours (A.M.), Hôpital Bretonneau, Service de neurologie, Tours, France; Department of Neurology (M.K.), Alfried Krupp von Bohlen und Halbach Hospital, Essen; Department of Neurology (M.K.), Medical Faculty, Heinrich Heine University of Düsseldorf, Germany; Neurology Department (L.R.-P.), Multiple Sclerosis Unit, Hospital Universitari de Bellvitge, IDIBELL, Barcelona, Spain; Department of Neurology (T.M.), Tohoku University Hospital, Japan; Service de Neurologie (J.-C.O.), Pôle des Neurosciences Cliniques, CHU de Bordeaux Pellegrin Tripode; Service de Neurologie et Unité Neurovasculaire (M.P.G.), Centre Hospitalier Régional d'Orléans, France; Unit of Neuroradiology (S.G.), Papa Giovanni XXIII Hospital, Bergamo, Italy; Multiple Sclerosis Center (C.B.), Second Department of Neurology, Aristotle University of Thessaloniki, Greece; Servicio de Neurología (R.P.M.), Hospital Universitario Clínico San Cecilio, Granada, Spain; Department of Neurology (B.V., I.J.), University Hospital Zurich and University of Zurich, ; Neurologic Clinic and Policlinic and Research Center for Clinical Neuroimmunology and Neuroscience (P.K., T.J.D.), Departments of Medicine, Biomedicine, and Clinical Research, University Hospital Basel, University of Basel, Switzerland; Service de Neurologie (X.M.), Université Clermont Auvergne, CHU de Clermont-Ferrand, Inserm, Neuro-Dol; Infectious and Tropical Diseases Unit (G.M.-B.), University Hospital of Toulouse, France; Department of Neurology (C.M.), State University of New York Upstate Medical University, Syracuse; and CHU Nantes (D.A.L.), Service de Neurologie, CRC-SEP, Nantes Université, INSERM, CIC 1413, Center for Research in Transplantation and Translational Immunology, UMR 1064, France.

Neurology(R) Neuroimmunology & Neuroinflammation
|July 11, 2024
PubMed
Abstract

Insights

Sphingosine-1-phosphate receptor modulators (S1P-RMs) and natalizumab treatments for multiple sclerosis (MS) carry risks of progressive multifocal leukoencephalopathy (PML). S1P-RM-associated PML presents differently and has lower IRIS risk but increased MS activity post-treatment.

Area of Science:

  • Neurology
  • Immunology
  • Infectious Diseases

Background:

  • Progressive multifocal leukoencephalopathy (PML) is a severe opportunistic infection caused by JC virus reactivation in immunocompromised individuals.
  • Certain multiple sclerosis (MS) disease-modifying therapies (DMTs), including natalizumab and sphingosine-1-phosphate receptor modulators (S1P-RMs), are associated with an increased risk of PML.
  • While natalizumab-associated PML is well-characterized, data on S1P-RM-associated PML remain limited.

Purpose of the Study:

  • To compare the clinical presentations and outcomes of PML in patients treated with S1P-RMs versus natalizumab.
  • To identify differences in disease characteristics, immune reconstitution inflammatory syndrome (IRIS) development, and post-PML disease activity between the two treatment groups.

Main Methods:

  • A retrospective multicenter cohort study included patients diagnosed with PML between 2009 and 2022.
  • Patients were stratified based on prior treatment with S1P-RMs or natalizumab.
  • Data analyzed included clinical and radiologic presentation, IRIS, survival, disability (modified Rankin Scale - mRS), and MS relapses post-PML.

Main Results:

  • Of 84 analyzed patients, 20 received S1P-RMs and 64 received natalizumab.
  • S1P-RM-associated PML occurred in older patients with longer treatment durations and presented with more disseminated lesions and higher gadolinium enhancement.
  • Natalizumab-treated patients had a higher incidence of IRIS, while S1P-RM patients exhibited significantly higher post-treatment MS activity.

Conclusions:

  • PML associated with S1P-RMs differs in presentation and IRIS risk compared to natalizumab-associated PML.
  • Higher post-treatment MS activity in the S1P-RM group necessitates careful management strategies.
  • Treatment decisions post-PML should consider the patient's prior DMT, guiding tailored therapeutic approaches.

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