{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T14:09:18Z","timestamp":1761919758371},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,2,12]],"date-time":"2014-02-12T00:00:00Z","timestamp":1392163200000},"content-version":"vor","delay-in-days":42,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To identify cases of laboratory\u2010 or biopsy\u2010confirmed 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We searched the US Food and Drug Administration Adverse Event Reporting System and MEDLINE for reports submitted from 2006 to 2012 of laboratory\u2010confirmed PML with symptom onset \u226530 days following NTZ withdrawal. We only analyzed cases where NTZ discontinuation was unrelated to suspected PML.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u2009=\u20099\u201359 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 \u22651 PML risk factor, including NTZ duration \u22652 years (n\u2009=\u200913), prior immunosuppressive agents (n\u2009=\u20098), and reported anti\u2013JC virus seropositivity (n\u2009=\u200913).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>NTZ\u2010treated patients presenting clinically with PML within 6 months after NTZ withdrawal frequently have pre\u2010existing 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\u2013115<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.24051","type":"journal-article","created":{"date-parts":[[2013,11,16]],"date-time":"2013-11-16T11:29:05Z","timestamp":1384601345000},"page":"108-115","source":"Crossref","is-referenced-by-count":45,"title":["Progressive multifocal leukoencephalopathy after natalizumab discontinuation"],"prefix":"10.1002","volume":"75","author":[{"given":"Andrew J.","family":"Fine","sequence":"first","affiliation":[{"name":"Office of Surveillance and Epidemiology Center for Drug Evaluation and Research, US Food and Drug Administration Silver Spring MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfred","family":"Sorbello","sequence":"additional","affiliation":[{"name":"Office of Surveillance and Epidemiology Center for Drug Evaluation and Research, US Food and Drug Administration Silver Spring MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cindy","family":"Kortepeter","sequence":"additional","affiliation":[{"name":"Office of Surveillance and Epidemiology Center for Drug Evaluation and Research, US Food and Drug Administration Silver Spring MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Scarazzini","sequence":"additional","affiliation":[{"name":"Current address for Dr Scarazzini: Global Pharmacovigilance AbbVie, Inc North Chicago IL 60064"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,2,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e328360279f"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20858"},{"key":"e_1_2_7_4_1","volume-title":"Package insert","author":"Tysabri","year":"2012"},{"key":"e_1_2_7_5_1","unstructured":"MedDRA\u00aeis a registered trademark of the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA). International Federation of Pharmaceutical Manufacturers and Associations. Geneva Switzerland: Medical Dictionary for Regulatory Activities (MedDRA)."},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70028-4"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318253d61e"},{"key":"e_1_2_7_8_1","unstructured":"MoiolaL SangalliM RadaelliG et al.A case of progressive multifocal leukoencephalopathy after discontinuation of natalizumab: when could we let the guard down. Paper presented at: 5th Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis; October 21 2011; Amsterdam the Netherlands."},{"key":"e_1_2_7_9_1","unstructured":"RoggeroneS Duran\u2010DubiefF ChenevierF et al.Remain vigilant after natalizumab discontinuation: three remarkable cases. Paper presented at: 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis; October 10\u201313 2012; Lyon France. AbstractP538."},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458512466165"},{"key":"e_1_2_7_11_1","unstructured":"MusukaTD CarollWM.Natalizumab\u2010to\u2010fingolimod transition PML and PML\u2010IRIS: management conundrum and insights. Poster presented at: Australian and New Zealand Association of Neurologists Annual Scientific Meeting; October 7 2012; Perth Australia."},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000341766.59028.9d"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70149-1"},{"key":"e_1_2_7_14_1","first-page":"S507","article-title":"Effects of a 24\u2010week natalizumab treatment interruption on clinical and radiologic parameters of multiple sclerosis disease activity: the RESTORE study","volume":"17","author":"Fox R","year":"2011","journal-title":"Mult Scler"},{"key":"e_1_2_7_15_1","first-page":"P05.047","volume-title":"The kinetics of CSF lymphocyte recovery after cessation of natalizumab in patients with multiple sclerosis","author":"Javed A","year":"2010"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182768983"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1107829"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458511435105"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/practneurol-2011-000092"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.24051","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.24051","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T16:44:34Z","timestamp":1696610674000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.24051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1]]},"references-count":18,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014,1]]}},"alternative-id":["10.1002\/ana.24051"],"URL":"https:\/\/doi.org\/10.1002\/ana.24051","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1]]}}}