Natalizumab-related PML 2 weeks after negative anti-JCV antibody assay

Brosseau, Marie Sarah Gagne; Stobbe, Gary; Wundes, Annette

doi:10.1212/wnl.0000000000002330

Cited by 31 publications

(12 citation statements)

References 5 publications

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“…For patients with MS, JCV serostatus is a known risk factor for natalizumab-induced PML; it is unknown whether JCV serostatus is an important risk factor for other vulnerable populations, such as those with hematologic malignancies. 17,18 When monoclonal antibodies were introduced in the treatment of MS, and as patients started to develop PML, immunosuppressive algorithms were constructed to stratify the risk potential for PML and consensus guidelines detailed the timing of periodic anti-JCV antibody testing. Biomarkers, such as the anti-JCV antibody index, are being investigated to identify MS patients at greatest risk of developing PML and to direct the use of immunomodulating therapy.…”

Section: Discussionmentioning

confidence: 99%

“…19,20 These biomarkers have not been validated in other conditions, and the significance and utility of JCV testing in patients with hematologic malignancies have not been investigated but warrant study, especially in those receiving chronic immunosuppressive treatment. 3,9,18 Prevention is valuable, because the condition is almost universally fatal. 1 In a review of 57 HIV-negative lymphoma patients treated with rituximab who developed PML, there was a 90% fatality rate within a median survival of 2.0 months.…”

Section: Discussionmentioning

confidence: 99%

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Progressive multifocal leukoencephalopathy and hematologic malignancies: a single cancer center retrospective review

Neil

DeAngelis

2017

Blood Advances

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Progressive multifocal leukoencephalopathy and hematologic malignancies: a single cancer center retrospective review

Neil

DeAngelis

2017

Blood Advances

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“…Our data suggest that an older age at NTZ start might be a risk factor for developing PML before 24 infusions. Interestingly, advanced age has been reported to be also a risk factor for PML under other MS therapies, such as fingolimod and dimethyl fumarate [44], suggesting that age may represents an additional risk stratifier for PML in patients treated with MS therapeutics.…”

Section: Discussionmentioning

confidence: 99%

Natalizumab-Related Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis: Findings from an Italian Independent Registry

et al. 2016

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BackgroundThe monoclonal antibody natalizumab (NTZ) is a highly effective treatment for patients with multiple sclerosis (MS). However, this drug is associated with increased risk of developing Progressive Multifocal Leukoencephalopathy (PML), an opportunistic infection of central nervous system (CNS) caused by the John Cunningham polyomavirus (JCV).ObjectiveTo describe the 12-month clinical course of 39 patients with MS (28 women, 11 men) who developed NTZ-related PML after a mean exposure of 39 infusions.MethodsAn Italian independent collaborative repository initiative collected and analyzed socio-demographic, clinical, magnetic resonance imaging (MRI) data and number of JCV-DNA copies detected on cerebrospinal fluid (CSF) samples of patients diagnosed as affected by NTZ-related PML. The evolution of disability, measured by the Expanded Disability Status Scale, was assessed at NTZ start, at PML diagnosis and after 2, 6 and 12 months from PML diagnosis. The effect of clinical and paraclinical characteristics at PML diagnosis on the final outcome was also investigated.ResultsTen patients (25.6%) were diagnosed before 24 NTZ infusions. In six cases (15.4%) the PML suspect was made on the basis of highly suggestive MRI findings in absence of any detectable change of clinical conditions (asymptomatic PML). In patients with symptomatic PML, the diagnosis was quicker for those who presented with cognitive symptoms (n = 12) rather than for those with other neurological pictures (n = 21) (p = 0.003). Three patients (7.7%) died during the 12-month observation period, resulting in a survival rate of 92.3%. Asymptomatic PML, more localized brain involvement and gadolinium-enhancement detected at MRI, as well as lower viral load were associated with a better disability outcome (p-values<0.01).ConclusionOur findings support that early PML diagnosis, limited CNS involvement and initial signs of immune restoration are associated with a better outcome and higher survival rate, and confirm the utility of MRI as a surveillance tool for NTZ-treated patients.

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“…Also Plavina et al [] proposed a cut‐off for anti‐JCV antibodies, where indexes higher than 1.5 absorbance OD units could indicate higher risk for PML. Although these data may be used to stratify patients at risk of PML, it might not be a very useful tool to actually predict PML, since not always the anti‐JCV antibodies titers is related with duration of NTZ exposure and PML onset [Antoniol and Stankoff ; Plavina et al, ; Gagne Brosseau et al, ]. Most strikingly, a patient without previous immunosuppressive therapy who developed PML presented no anti‐JCV antibodies until 2 weeks before PML onset [Gagne Brosseau et al, ].…”

Section: Discussionmentioning

confidence: 99%

Polyomavirus detection in multiple sclerosis patients under natalizumab therapy: Profile and frequency of urinary shedding

Nali

Fink

Olival

et al. 2016

Journal of Medical Virology

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Patients undergoing Natalizumab (NTZ) therapy are at risk of progressive multifocal leukoencephalopathy (PML). Besides John Cunningham virus (JCV), BK polyomavirus might represent an additional concern for such patients since it can also infect CNS cells. Currently, data regarding the presence of anti-JCV antibodies added to previous immunosuppressive therapy and prolonged NTZ therapy has been used to classify patients at risk of developing PML. Here, we investigated the profile shedding of JCV and BKV in multiple sclerosis (MS) patients during treatment with NTZ. Serial blood and urine samples from 97 MS patients receiving either NTZ or β-interferon were investigated for polyomavirus shedding. While all blood samples tested negative, 36% of the patients shed polyomavirus in the urine in at least one time point. From these, 21.7%, 9.3%, and 5.1% shed JCV, BKV, and both polyomavirus, respectively. No difference was observed between the rates of urinary shedding of patients treated with NTZ (38.9%) and patients treated with other drugs (34.5%), also no PML event was diagnosed during the follow-up. Therefore, urinary shedding might not be interfered by therapy condition. In our study, we also observed 14/27 (52%) of anti-JCV antibodies prevalence, and nearly half of them (42%) did not present any event of urinary shedding during the follow-up. J. Med. Virol. 89:528-534, 2017. © 2016 Wiley Periodicals, Inc.

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Natalizumab-related PML 2 weeks after negative anti-JCV antibody assay

Cited by 31 publications

References 5 publications

Progressive multifocal leukoencephalopathy and hematologic malignancies: a single cancer center retrospective review

Progressive multifocal leukoencephalopathy and hematologic malignancies: a single cancer center retrospective review

Natalizumab-Related Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis: Findings from an Italian Independent Registry

Polyomavirus detection in multiple sclerosis patients under natalizumab therapy: Profile and frequency of urinary shedding

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