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Conference/Presentation Title: | Increased john cunningham virus seroconversion rates seen in a southern hemisphere international cohort of natalizumab treated patients. | Authors: | Dwyer C.;Butler E. ;Haartsen J.;Butzkueven H.;Cartwright A.;Shuey N.;Coleman J. ;Macdonell R.;Rath L.;Fragoso Y.;Van Der Walt A.;Carey J.;Kilpatrick T.;Jokubaitis V.;Stankovich J.;Baker J.;Fryer K. | Monash Health Department(s): | Neurology Urology |
Institution: | (Dwyer, Baker, Carey, Kilpatrick) Melbourne Brain Centre, Royal Melbourne Hospital (Jokubaitis, Stankovich, Butzkueven, Van Der Walt) Dept of Neuroscience, Monash University (Jokubaitis, Butzkueven, Rath, Van Der Walt) Dept of Neurology, Alfred Hospital (Kilpatrick) Melbourne Neuroscience Institute, University of Melbourne (Fryer, Butler) Dept of Neurology, Monash Medical Centre (Haartsen, Butzkueven) Eastern Clinical Research Unit, Box Hill Hospital (Cartwright, Shuey) St Vincent's Hospital (Coleman, Macdonell) Austin Health (Fragoso) Universidade Metropolitana de Santos | Presentation/Conference Date: | 14-Oct-2020 | Copyright year: | 2020 | Publisher: | Lippincott Williams and Wilkins | Publication information: | Neurology. Conference: 72nd Annual Meeting of the American Academy of Neurology, AAN 2020. Toronto, ON Canada. 94 (15 Supplement) (no pagination), 2020. Date of Publication: 2020. | Abstract: | Objective: To assess factors associated with John Cunningham virus (JCV) seroconversion in natalizumab-treated patients. Background(s): Natalizumab is a highly effective treatment for relapsing-remitting multiple sclerosis (RRMS), but its use is complicated by JCV co-infection. This virus can result in progressive multifocal leukoencephalopathy (PML), a devastating infection of the central nervous system. Serial assessment of JCV serostatus is therefore mandated during natalizumab treatment Design/Methods: Patients treated with natalizumab for RRMS at six tertiary hospitals in Melbourne, Australia (n=869) and eleven MS treatment centres in Brazil (n=137) were assessed for change in JCV serostatus, duration of natalizumab exposure and prior immunosuppression. Sensitivity analyses examined whether sex, age, hospital, prior immunosuppression or number of JCV tests affected time to seroconversion. Result(s): From a cohort of 1001 natalizumab-treated patients (510 with multiple measures of JCV serostatus), 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 (3.9%) patients had fluctuating serostatus. Time-to-event analysis did not identify a relationship between JCV seroconversion and duration of natalizumab exposure or prior immunosuppressive use. Male sex was associated with a greater risk of JCV seroconversion (adjusted hazard ratio 2.09 (95% CI 1.17-3.71) p=0.012). Conclusion(s): In this large cohort of natalizumab-treated patients we observed durable positive seroconversion at an annualised rate of 7.3%. This rate exceeds that noted in registration and post-marketing studies for natalizumab and is consistent with increased rates of seroconversion reported recently by European centres. This rate also greatly exceeds that predicted by epidemiological studies of JCV seroconversion in healthy populations. Taken together, our finding supports emerging evidence that natalizumab causes off-target immune system changes that may be trophic for JCV seroconversion. In addition, male sex may be associated with an increased risk of positive JCV seroconversion. | Conference Start Date: | 2020-04-25 | Conference End Date: | 2020-05-01 | ISSN: | 1526-632X | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/35061 | Type: | Conference Abstract | Subjects: | female adult Australia Brazil *cohort analysis conference abstract controlled study drug combination drug therapy human immunomodulation immunosuppressive treatment *JC virus major clinical study male multicenter study multiple sclerosis nonhuman postmarketing surveillance remission sensitivity analysis *seroconversion *Southern Hemisphere tertiary care center *natalizumab *JC virus major clinical study male multicenter study multiple sclerosis nonhuman postmarketing surveillance remission sensitivity analysis *seroconversion conference abstract tertiary care center *cohort analysis Brazil Australia adult *Southern Hemisphere controlled study drug combination drug therapy female human immunomodulation immunosuppressive treatment |
Type of Clinical Study or Trial: | Observational study (cohort, case-control, cross sectional or survey) |
Appears in Collections: | Conferences |
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