TY - JOUR
T1 - Outcome Predictors in Progressive Multifocal Leukoencephalopathy Associated With Multiple Sclerosis Treatments
T2 - A Multicenter Cohort Study
AU - CORPUS and Italian PML study groups
AU - Blant, Julie Céline
AU - De Rossi, Nicola
AU - Gold, Ralf
AU - Maurousset, Aude
AU - Kraemer, Markus
AU - Romero-Pinel, Lucía
AU - Misu, Tatsuro
AU - Ouallet, Jean Christophe
AU - Pallix Guyot, Maud
AU - Gerevini, Simonetta
AU - Bakirtzis, Christos
AU - Piñar Morales, Raquel
AU - Vlad, Benjamin
AU - Karypidis, Panajotis
AU - Moisset, Xavier
AU - Derfuss, Tobias J.
AU - Jelcic, Ilijas
AU - Martin-Blondel, Guillaume
AU - Ayzenberg, Ilya
AU - McGraw, Corey
AU - Laplaud, David Axel
AU - Lebrun-Frenay, Christine
AU - Du Pasquier, Renaud A.
AU - Bernard-Valnet, Raphael
PY - 2026/5/1
Y1 - 2026/5/1
N2 - BACKGROUND AND OBJECTIVES: JC virus (JCV) reactivation causing progressive multifocal leukoencephalopathy (PML) is a complication in patients with multiple sclerosis (MS) treated with disease-modifying therapies (DMTs). Although natalizumab (NTZ) is most frequently involved, PML also occurs less commonly with sphingosine-1-phosphate receptor modulators (S1P-RM), dimethyl fumarate (DMF), and ocrelizumab. This study aimed to identify factors predicting worse outcomes, focusing on the influence of PML-immune reconstitution inflammatory syndrome (PML-IRIS), plasma exchange (PlEx), corticosteroids, and DMT reintroduction. METHODS: This retrospective multicenter cohort study analyzed patients with MS who had JCV-associated pathology (PML or granule cell neuronopathy) from 42 centers (2009-2022). The primary outcome was disability at 12 months, measured by the modified Rankin Scale (mRS). Multivariable analyses identified predictors of poor outcomes, PML-IRIS development, and recurrent MS activity. RESULTS: Of 96 identified patients, 94 were analyzed. Most cases occurred under NTZ (77%), followed by S1P-RM (22%) and DMF (1%). Twelve-month survival was 91.5%, with a median mRS of 3 [IQR: 2-4]. Multivariable analysis showed that higher pre-PML disability (OR: 1.95 [95% CI 1.46-2.60], p < 0.001), elevated CSF JCV viral load (OR: 2.45 [95% CI 1.55-3.87], p < 0.001), and symptomatic presentation at onset (OR: 3.93 [95% CI 1.23-12.55], p = 0.021) were associated with worse outcomes. Conversely, PML-IRIS was associated with better outcomes (OR: 0.28 [95% CI 0.09-0.86], p = 0.025). PlEx and corticosteroid use had no negative effect. DISCUSSION: This study provides valuable insights into the management of iatrogenic PML in patients with MS. The findings may guide clinicians in making informed decisions, particularly regarding the use of PlEx, corticosteroids, and the management of PML-IRIS.
AB - BACKGROUND AND OBJECTIVES: JC virus (JCV) reactivation causing progressive multifocal leukoencephalopathy (PML) is a complication in patients with multiple sclerosis (MS) treated with disease-modifying therapies (DMTs). Although natalizumab (NTZ) is most frequently involved, PML also occurs less commonly with sphingosine-1-phosphate receptor modulators (S1P-RM), dimethyl fumarate (DMF), and ocrelizumab. This study aimed to identify factors predicting worse outcomes, focusing on the influence of PML-immune reconstitution inflammatory syndrome (PML-IRIS), plasma exchange (PlEx), corticosteroids, and DMT reintroduction. METHODS: This retrospective multicenter cohort study analyzed patients with MS who had JCV-associated pathology (PML or granule cell neuronopathy) from 42 centers (2009-2022). The primary outcome was disability at 12 months, measured by the modified Rankin Scale (mRS). Multivariable analyses identified predictors of poor outcomes, PML-IRIS development, and recurrent MS activity. RESULTS: Of 96 identified patients, 94 were analyzed. Most cases occurred under NTZ (77%), followed by S1P-RM (22%) and DMF (1%). Twelve-month survival was 91.5%, with a median mRS of 3 [IQR: 2-4]. Multivariable analysis showed that higher pre-PML disability (OR: 1.95 [95% CI 1.46-2.60], p < 0.001), elevated CSF JCV viral load (OR: 2.45 [95% CI 1.55-3.87], p < 0.001), and symptomatic presentation at onset (OR: 3.93 [95% CI 1.23-12.55], p = 0.021) were associated with worse outcomes. Conversely, PML-IRIS was associated with better outcomes (OR: 0.28 [95% CI 0.09-0.86], p = 0.025). PlEx and corticosteroid use had no negative effect. DISCUSSION: This study provides valuable insights into the management of iatrogenic PML in patients with MS. The findings may guide clinicians in making informed decisions, particularly regarding the use of PlEx, corticosteroids, and the management of PML-IRIS.
UR - https://www.scopus.com/pages/publications/105030785850
U2 - 10.1212/NXI.0000000000200558
DO - 10.1212/NXI.0000000000200558
M3 - Article
C2 - 41719500
SN - 2332-7812
VL - 13
SP - e200558
JO - Neurology: Neuroimmunology and NeuroInflammation
JF - Neurology: Neuroimmunology and NeuroInflammation
IS - 3
ER -