Progressive multifocal leukoencephalopathy after natalizumab discontinuation
Andrew J Fine1, Alfred Sorbello, Cindy Kortepeter
1Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD.
Annals of Neurology
|November 19, 2013
Summary
Patients discontinuing natalizumab (NTZ) for multiple sclerosis (MS) can develop progressive multifocal leukoencephalopathy (PML) within six months. Many cases have pre-existing PML risk factors, requiring clinician awareness.
Area of Science:
- Neurology
- Immunology
Background:
- Natalizumab (NTZ) is an effective treatment for multiple sclerosis (MS).
- Discontinuation of NTZ can be followed by opportunistic infections, including progressive multifocal leukoencephalopathy (PML).
Purpose of the Study:
- To identify cases of laboratory- or biopsy-confirmed progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis (MS) who previously discontinued natalizumab (NTZ) for reasons unrelated to suspected or proven PML.
- To assess PML risk factors in these identified cases.
Main Methods:
- Searched US Food and Drug Administration Adverse Event Reporting System and MEDLINE for reports from 2006-2012.
- Included laboratory-confirmed PML cases with symptom onset ≥30 days post-NTZ withdrawal, where discontinuation was unrelated to suspected PML.
Main Results:
- Identified 17 patients with PML after NTZ discontinuation for non-PML reasons; median NTZ duration was 47 doses.
- PML was confirmed within 6 months of withdrawal; 11 patients experienced immune reconstitution inflammatory syndrome (IRIS).
- At NTZ withdrawal, 94% had ≥1 PML risk factor, including NTZ duration ≥2 years (n=13), prior immunosuppressants (n=8), and anti-JC virus seropositivity (n=13).
Conclusions:
- Patients discontinuing NTZ for MS may develop PML within 6 months, often with pre-existing risk factors.
- Heightened clinical awareness for PML, IRIS, and MS relapse is crucial when evaluating neurological decline post-NTZ discontinuation.
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