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Outcome Predictors in Progressive Multifocal Leukoencephalopathy Associated With Multiple Sclerosis Treatments: A
Julie Céline Blant1, Nicola De Rossi2, Ralf Gold3
1Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital (Centre Hospitalier Universitaire Vaudois) and University of Lausanne, Switzerland.
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.
Insights
Higher pre-PML disability, elevated CSF JCV viral load, and symptomatic onset predict worse outcomes in multiple sclerosis patients with progressive multifocal leukoencephalopathy (PML). PML-immune reconstitution inflammatory syndrome (PML-IRIS) is linked to better outcomes.
Area of Science:
- Neurology
- Infectious Diseases
- Immunology
Background:
- Progressive multifocal leukoencephalopathy (PML) is a rare but serious complication of disease-modifying therapies (DMTs) for multiple sclerosis (MS).
- JC virus (JCV) reactivation triggers PML, with natalizumab (NTZ) being the most common associated DMT, but other DMTs like sphingosine-1-phosphate receptor modulators (S1P-RM), dimethyl fumarate (DMF), and ocrelizumab are also implicated.
- Identifying factors influencing PML outcomes is crucial for managing MS patients undergoing DMT.
Purpose of the Study:
- To identify predictors of worse outcomes in patients with MS-associated PML.
- To investigate the impact of PML-immune reconstitution inflammatory syndrome (PML-IRIS), plasma exchange (PlEx), corticosteroids, and DMT reintroduction on PML prognosis.
- To analyze factors associated with PML-IRIS development and recurrent MS activity.
Main Methods:
- A retrospective multicenter cohort study included 94 MS patients with JCV-associated PML or granule cell neuronopathy from 42 centers (2009-2022).
- The primary outcome was disability at 12 months, assessed using the modified Rankin Scale (mRS).
- Multivariable analyses were performed to identify predictors of poor outcomes, PML-IRIS, and recurrent MS activity.
Main Results:
- Higher pre-PML disability, elevated cerebrospinal fluid (CSF) JCV viral load, and symptomatic presentation at onset were significantly associated with worse 12-month outcomes.
- PML-IRIS was associated with significantly better outcomes.
- Plasma exchange (PlEx) and corticosteroid use did not demonstrate a negative impact on outcomes.
Conclusions:
- This study identifies key factors influencing PML prognosis in MS patients, including baseline disability, JCV viral load, and symptomatic onset.
- PML-IRIS appears to be a positive prognostic indicator.
- Findings can inform clinical decision-making regarding treatments like PlEx, corticosteroids, and management of PML-IRIS in iatrogenic PML.
