Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/26419
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dc.contributor.authorDwyer, Christopher M-
dc.contributor.authorJokubaitis, Vilija G-
dc.contributor.authorStankovich, Jim-
dc.contributor.authorBaker, Josephine-
dc.contributor.authorHaartsen, Jodi-
dc.contributor.authorButzkueven, Helmut-
dc.contributor.authorCartwright, Adriana-
dc.contributor.authorShuey, Neil-
dc.contributor.authorFragoso, Yara Dadalti-
dc.contributor.authorRath, Louise-
dc.contributor.authorSkibina, Olga-
dc.contributor.authorFryer, Kylie-
dc.contributor.authorButler, Ernest-
dc.contributor.authorColeman, Jennifer-
dc.contributor.authorMacIntrye, Jennifer-
dc.contributor.authorMacdonell, Richard A L-
dc.contributor.authorvan der Walt, Anneke-
dc.date2021-
dc.date.accessioned2021-05-10T07:13:19Z-
dc.date.available2021-05-10T07:13:19Z-
dc.date.issued2021-04-16-
dc.identifier.citationTherapeutic Advances in Neurological Disorders 2021; 14: 1756286421998915en
dc.identifier.issn1756-2856
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/26419-
dc.description.abstractTo retrospectively assess factors associated with John Cunningham virus (JCV) seroconversion in natalizumab-treated patients. Natalizumab is highly effective for the treatment of relapsing-remitting multiple sclerosis (RRMS), but its use is complicated by opportunistic JCV infection. This virus can result in progressive multifocal leukoencephalopathy (PML). Serial assessment of JCV serostatus is mandated during natalizumab treatment. Patients treated with natalizumab for RRMS at six tertiary hospitals in Melbourne, Australia (n = 865) and 11 MS treatment centres in Brazil (n = 136) were assessed for change in JCV serostatus, duration of exposure to natalizumab and prior immunosuppression. Sensitivity analyses examined whether sex, age, tertiary centre, prior immunosuppression or number of JCV tests affected time to seroconversion. From a cohort of 1001 natalizumab-treated patients, durable positive seroconversion was observed in 83 of 345 initially JCV negative patients (24.1%; 7.3% per year). Conversely, 16 of 165 initially JCV positive patients experienced durable negative seroconversion (9.7%; 3.8% per year). Forty patients (3.9%) had fluctuating serostatus. Time-to-event analysis did not identify a relationship between JCV seroconversion and duration of natalizumab exposure. Prior exposure to immunosuppression was not associated with an increased hazard of positive JCV seroconversion. Male sex was associated with increased JCV seroconversion risk [adjusted hazard ratio 2.09 (95% confidence interval 1.17-3.71) p = 0.012]. In this large international cohort of natalizumab-treated patients we observed an annual durable positive seroconversion rate of 7.3%. This rate exceeds that noted in registration and post-marketing studies for natalizumab. This rate also greatly exceeds that predicted by epidemiological studies of JCV seroconversion in healthy populations. Taken together, our findings support emerging evidence that natalizumab causes off-target immune changes that may be trophic for JCV seroconversion. In addition, male sex may be associated with increased positive JCV seroconversion.en
dc.language.isoeng
dc.subjectJohn Cunningham virusen
dc.subjectMultiple sclerosisen
dc.subjectnatalizumaben
dc.subjectseroconversionen
dc.titleHigh rates of JCV seroconversion in a large international cohort of natalizumab-treated patients.en
dc.typeJournal Articleen
dc.identifier.journaltitleTherapeutic Advances in Neurological Disordersen
dc.identifier.affiliationUniversidade Metropolitana de Santos, São Paulo, Brazilen
dc.identifier.affiliationDepartment of Neurology, Monash Health, Clayton, VC, Australiaen
dc.identifier.affiliationEastern Clinical Research Unit, Department of Neurology, Box Hill Hospital, Melbourne, VIC, Australiaen
dc.identifier.affiliationMelbourne Brain Centre, Royal Melbourne Hospital, Parkville, VC, Australiaen
dc.identifier.affiliationDepartment of Neuroscience, Monash University, Melbourne, VC, Australiaen
dc.identifier.affiliationMelbourne Brain Centre, Royal Melbourne Hospital, 300 Grattan Street, Parkville, VC 3050, Australiaen
dc.identifier.affiliationDepartment of Neuroscience, Monash University, 99 Commercial Rd, Melbourne, VC 3004, Australiaen
dc.identifier.affiliationNeurologyen
dc.identifier.affiliationDepartment of Neurology, The Alfred Hospital, Melbourne, VC, Australiaen
dc.identifier.affiliationDepartment of Neurology, St Vincent's Hospital, Melbourne, VIC, Australiaen
dc.identifier.doi10.1177/1756286421998915en
dc.type.contentTexten
dc.identifier.orcid0000-0001-6387-6585en
dc.identifier.orcid0000-0002-4278-7003en
dc.identifier.pubmedid33948117
local.name.researcherMacdonell, Richard A L
item.cerifentitytypePublications-
item.languageiso639-1en-
item.grantfulltextnone-
item.openairetypeJournal Article-
item.fulltextNo Fulltext-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
crisitem.author.deptNeurology-
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