Natalizumab-Associated Progressive Multifocal Leukoencephalopathy Risk Stratification
Summary
Natalizumab is a high-efficacy monoclonal antibody employed in the treatment of relapsing forms of multiple sclerosis. Its mechanism, which involves blockade of α4-integrin on lymphocytes, strongly reduces central nervous system inflammation but carries an elevated risk of progressive multifocal leukoencephalopathy (PML). PML is an opportunistic infection caused by reactivation of the John Cunningham virus (JCV) in immunosuppressed individuals, leading to demyelination and severe neurological decline. Risk stratification integrates factors such as JCV serostatus and antibody index, prior immunosuppressant use and treatment duration. Recent advances have introduced refined algorithms and biomarkers to individualise patient monitoring and guide treatment duration, balancing therapeutic benefit against PML risk. Improved surveillance has led to earlier detection of viral reactivation, informed decision-making on continuation or cessation of natalizumab, and alternative therapy strategies for high-risk patients. This approach aims to maximise long-term neurological stability while mitigating life-threatening complications.
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Natalizumab-Associated Progressive Multifocal Leukoencephalopathy Risk Stratification publication trend
The graph below shows the total number of articles in natalizumab-associated progressive multifocal leukoencephalopathy risk stratification across all publications each year (not limited to Nature Index journals).
Technical terms
Natalizumab: A monoclonal antibody targeting α4-integrin on leukocytes, used to limit immune cell migration into the central nervous system in multiple sclerosis.
Progressive multifocal leukoencephalopathy (PML): A demyelinating brain disease caused by reactivated John Cunningham virus in immunocompromised individuals.
John Cunningham virus (JCV): A common polyomavirus that remains latent in most people but can cause PML upon immune suppression.
Anti-JCV antibody index: A quantitative serological measure of JCV-specific antibodies used to stratify PML risk in natalizumab-treated patients.
Lipid-specific IgM oligoclonal bands: Immunoglobulin M bands detected in cerebrospinal fluid that reflect intrathecal lipid antigen reactivity and may predict PML susceptibility.
References
- Analysis of Immunological Memory for John Cunningham Virus in a Mexican Population of Patients with Multiple Sclerosis Under Treatment. Biomedicines (2024).
- Reduction of the risk of PML in natalizumab treated MS patients in Sweden: An effect of improved PML risk surveillance. Multiple Sclerosis and Related Disorders (2021).
- New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab. Frontiers in Neurology (2020).
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