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Induction and Clinical Scoring of Chronic-Relapsing Experimental Autoimmune Encephalomyelitis
Published on: July 4, 2007
Natalizumab-Associated Progressive Multifocal Leukoencephalopathy After Natalizumab Extended Interval Dosing Therapy
Kazuya Takahashi1,2, Jin Nakahara3, Yoshiharu Miura4
1Department of Neurology, Hokuriku Brain and Neuromuscular Disease Center, National Hospital Organization Iou National Hospital, Kanazawa, Japan.
Objective:
To describe 5 confirmed cases of natalizumab-associated progressive multifocal leukoencephalopathy (NTZ-PML) in Japan.
Methods:
The Nationwide PML Surveillance Committee requires mandatory registration of all natalizumab cases and reporting by affiliated facilities conducting JC DNA testing. Suspected PML cases were reviewed by the committee and classified as definite, probable, possible, or non-PML based on established diagnostic criteria.
Results:
From 2016 to 2024, the nationwide PML surveillance committee identified 8 NTZ-PML cases, of which 5 (all women and relapsing-remitting types) were registered as clinically definite PML cases. Four cases involved a switch from other disease-modifying drugs, while one involved natalizumab as the first-line treatment for multiple sclerosis (MS). In all cases, extended interval dosing therapy (EID) every 6-8 weeks was administered for at least 1 year before PML onset, and 3 cases had received EID from the outset. At PML onset, the viral DNA levels in the CSF were ≤100 copies/mL in 3 cases.
Discussion:
Given the high prevalence of JC virus antibody positivity in Japan, additional risk factors may contribute to NTZ-PML susceptibility. Although EID of natalizumab is expected to reduce PML risk, its effectiveness may be limited, particularly in Japanese individuals with high JC virus antibody titers.
Insights
Five cases of natalizumab-associated progressive multifocal leukoencephalopathy (NTZ-PML) were identified in Japan. Extended interval dosing (EID) may not fully mitigate PML risk in Japanese individuals with high JC virus antibody titers.
Area of Science:
- Neuroimmunology
- Infectious Neurology
- Pharmacovigilance
Background:
- Natalizumab is a disease-modifying therapy for multiple sclerosis (MS).
- Progressive multifocal leukoencephalopathy (PML) is a rare but serious adverse event associated with natalizumab treatment.
- JC virus (JCV) is the causative agent of PML.
Purpose of the Study:
- To describe confirmed cases of natalizumab-associated progressive multifocal leukoencephalopathy (NTZ-PML) in Japan.
- To evaluate the risk factors and clinical characteristics of NTZ-PML in a Japanese population.
Main Methods:
- Mandatory registration of natalizumab cases and JCV DNA testing by the Nationwide PML Surveillance Committee.
- Review and classification of suspected PML cases based on established diagnostic criteria.
- Analysis of clinical data, including treatment history, dosing regimens, and JCV DNA levels in cerebrospinal fluid (CSF).
Main Results:
- Five clinically definite NTZ-PML cases were identified between 2016 and 2024.
- All cases occurred in women with relapsing-remitting MS, with four switching from other disease-modifying drugs.
- Extended interval dosing (EID) every 6-8 weeks was used for at least one year prior to PML onset in all cases.
Conclusions:
- High JC virus antibody prevalence in Japan may indicate additional risk factors for NTZ-PML.
- The effectiveness of natalizumab EID in reducing PML risk may be limited in Japanese individuals with high JCV antibody titers.
- Further research is needed to understand NTZ-PML susceptibility in the Japanese population.
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