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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.
Background And Objectives:
Progressive multifocal leukoencephalopathy (PML) is a severe neurologic disease resulting from JC virus reactivation in immunocompromised patients. Certain multiple sclerosis (MS) disease-modifying therapies (DMTs) are associated with PML risk, such as natalizumab and, more rarely, sphingosine-1-phosphate receptor modulators (S1P-RMs). Although natalizumab-associated PML is well documented, information on S1P-RM-associated PML is limited. The aim of this study is to compare clinical presentations and outcomes between the 2 groups.
Methods:
A retrospective multicenter cohort study included patients with PML from 2009 to 2022 treated with S1P-RMs or natalizumab. Data on clinical and radiologic presentation, outcomes, immune reconstitution inflammatory syndrome (IRIS), survival, disability (using the modified Ranking scale-mRS), and MS relapses post-PML were analyzed.
Results:
Of 88 patients, 84 were analyzed (20 S1P-RM, 64 natalizumab). S1P-RM-associated PML was diagnosed in older patients (median age 52 vs 44 years, p < 0.001) and after longer treatment duration (median 63.9 vs 40 months, p < 0.001). Similarly, S1P-RM patients were more prone to show symptoms at diagnosis (100 vs 80.6%, p = 0.035), had more disseminated lesions (80% vs 34.9%, p = 0.002), and had higher gadolinium enhancement (65% vs 39.1%, p = 0.042). Natalizumab patients had a higher IRIS development rate (OR: 8.3 [1.92-33.3]). Overall, the outcome (mRS) at 12 months was similar in the 2 groups (OR: 0.81 [0.32-2.0]). Yet, post-treatment MS activity was higher in S1P-RM cases (OR: 5.7 [1.4-22.2]).
Discussion:
S1P-RM-associated PML shows reduced IRIS risk but higher post-treatment MS activity. Clinicians should tailor post-PML treatment based on pre-PML medication.
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