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

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...

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Detalles Bibliográficos
Autores: Blant, Julie C., Rossi, Nicola N. de, Gold, Ralf, Maurousset, Aude, Kraemer, Markus, Romero Pinel, Lucía María, Misu, Tatsuro, Ouallet, Jean Christophe, Pallix Guyot, Maud, Gerevini, Simonetta, Bakirtzis, Christos, Piñar Morales, Raquel, Vlad, Benjamin, Karypidis, Panajotis, Moisset, Xavier, Derfuss, Tobias J., Jelcic, Ilijas, Martin Blondel, Guillaume, Ayzenberg, Ilya, Mcgraw, Corey, Laplaud, David A., Du Pasquier, Renaud A., Bernard Valnet, Raphael, CORPUS, Italian PML study groups
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/224892
Acceso en línea:https://hdl.handle.net/2445/224892
Access Level:acceso abierto
Palabra clave:Esclerosi múltiple
Immunosupressió
Interferó
Multiple sclerosis
Immunosuppression
Interferon
Descripción
Sumario: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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