Original Article

Progressive multifocal leukoencephalopathy after natalizumab discontinuation

Corresponding Author

Andrew J. Fine PharmD, BCPS

Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD

Address correspondence to Dr Fine, US Food and Drug Administration, Center for Drug Evaluation and Research, 10903 New Hampshire Avenue, Silver Spring, MD 20993. E-mail: [email protected]Search for more papers by this author

Alfred Sorbello DO, MPH,

Alfred Sorbello DO, MPH

Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD

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Cindy Kortepeter PharmD,

Cindy Kortepeter PharmD

Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD

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Linda Scarazzini MD, RPh,

Linda Scarazzini MD, RPh

Current address for Dr Scarazzini: Global Pharmacovigilance, AbbVie, Inc, North Chicago, IL, 60064

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Andrew J. Fine PharmD, BCPS,

Corresponding Author

Andrew J. Fine PharmD, BCPS

Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD

Alfred Sorbello DO, MPH,

Alfred Sorbello DO, MPH

Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD

Search for more papers by this author

Cindy Kortepeter PharmD,

Cindy Kortepeter PharmD

Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD

Search for more papers by this author

Linda Scarazzini MD, RPh,

Linda Scarazzini MD, RPh

Current address for Dr Scarazzini: Global Pharmacovigilance, AbbVie, Inc, North Chicago, IL, 60064

Search for more papers by this author

First published: 16 November 2013

https://doi.org/10.1002/ana.24051

Citations: 45

The views expressed are those of the authors and do not necessarily represent those of, nor imply endorsement from, the US Food and Drug Administration or the US government.

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Abstract

Objective

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 and assess PML risk factors in these cases.

Methods

We searched the US Food and Drug Administration Adverse Event Reporting System and MEDLINE for reports submitted from 2006 to 2012 of laboratory-confirmed PML with symptom onset ≥30 days following NTZ withdrawal. We only analyzed cases where NTZ discontinuation was unrelated to suspected PML.

Results

Seventeen patients discontinued NTZ for reasons unrelated to PML but were subsequently diagnosed with the disease. The median NTZ duration was 47 monthly doses (range = 9–59 doses). All patients presented with compatible clinical symptoms within 6 months following withdrawal, and PML was confirmed by brain biopsy or by identifying JC virus in the cerebrospinal fluid by polymerase chain reaction. Immune reconstitution inflammatory syndrome (IRIS) was reported in 11 patients. Eleven patients (65%) received new MS treatments between NTZ discontinuation and PML confirmation. No deaths were reported. At NTZ withdrawal, 16 patients (94%) had ≥1 PML risk factor, including NTZ duration ≥2 years (n = 13), prior immunosuppressive agents (n = 8), and reported anti–JC virus seropositivity (n = 13).

Interpretation

NTZ-treated patients presenting clinically with PML within 6 months after NTZ withdrawal frequently have pre-existing PML risk factors. Clinicians need heightened awareness for new onset PML, IRIS, and MS relapse in evaluating neurological decline following NTZ discontinuation. Ann Neurol 2014;75:108–115

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Volume75, Issue1

January 2014

Pages 108-115

Progressive multifocal leukoencephalopathy after natalizumab discontinuation

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Progressive multifocal leukoencephalopathy after natalizumab discontinuation

Abstract

Objective

Methods

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Interpretation

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Citing Literature

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