High rates of JCV seroconversion in a large international cohort of natalizumab-treated patients.
John Cunningham virus
Multiple sclerosis
natalizumab
seroconversion
Journal
Therapeutic advances in neurological disorders
ISSN: 1756-2856
Titre abrégé: Ther Adv Neurol Disord
Pays: England
ID NLM: 101480242
Informations de publication
Date de publication:
2021
2021
Historique:
received:
10
01
2021
accepted:
17
01
2021
entrez:
5
5
2021
pubmed:
6
5
2021
medline:
6
5
2021
Statut:
epublish
Résumé
To 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 ( 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) 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.
Sections du résumé
AIMS
OBJECTIVE
To retrospectively assess factors associated with John Cunningham virus (JCV) seroconversion in natalizumab-treated patients.
BACKGROUND
BACKGROUND
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.
METHODS
METHODS
Patients treated with natalizumab for RRMS at six tertiary hospitals in Melbourne, Australia (
RESULTS
RESULTS
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)
CONCLUSION
CONCLUSIONS
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.
Identifiants
pubmed: 33948117
doi: 10.1177/1756286421998915
pii: 10.1177_1756286421998915
pmc: PMC8053827
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1756286421998915Informations de copyright
© The Author(s), 2021.
Déclaration de conflit d'intérêts
Conflict of interest statement: The authors declare that there is no conflict of interest.
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