Anti‐John Cunnigham virus antibody prevalence in multiple sclerosis patients: Baseline results of STRATIFY‐1

Bozic, Carmen; Richman, Sandra; Plavina, Tatiana; Natarajan, Amy; Scanlon, James; Subramanyam, Meena; Sandrock, Alfred; Bloomgren, Gary

doi:10.1002/ana.22606

Cited by 126 publications

(120 citation statements)

References 21 publications

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“…JCV is ubiquitous in human population and can be as prevalent as 80% according to some studies 21,22,23,24,25 . It is important to remind that JCV establishes latency in urinary tract and may be excreted during life without any consequence.…”

Section: Natalizumab and Pmlmentioning

confidence: 99%

Natalizumab treatment for multiple sclerosis: updates and considerations for safer treatment in JCV positive patients

Nali

Moraes

Fink

et al. 2014

Arq. Neuro-Psiquiatr.

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Natalizumab is currently one of the best options for treatment of patients with Multiple Sclerosis who have failed traditional prior therapies. However, prolonged use, prior immunosuppressive therapy and anti-JCV antibody status have been associated with increased risk of developing progressive multifocal leukoencephalopathy (PML). The evaluation of these conditions has been used to estimate risks of PML in these patients, and distinct (sometimes extreme) approaches are used to avoid the PML onset. At this time, the biggest issue facing the use of Natalizumab is how to get a balance between the risks and the benefits of the treatment. Hence, strategies for monitor JCV-positive patients undergoing Natalizumab treatment are deeply necessary. To illustrate it, we monitored JCV/DNA in blood and urine of a patient receiving Natalizumab for 12 months. We also bring to discussion the effectiveness of the current methods used for risk evaluation, and the real implications of viral reactivation.Keywords: multiple sclerosis, Natalizumab, JCV, risk factors, progressive multifocal leucoencephalopaty, viruria. RESUMO Natalizumabe é atualmente uma das melhores opções para o tratamento de pacientes com Esclerose Múltipla que não respondem aos tratamentos tradicionais. No entanto, o seu uso prolongado, o uso de terapia imunossupressora prévia e o status sorológico antivírus JC têm sido associados com o risco aumentado de desenvolvimento de Leucoencefalopatia Multifocal Progressiva (LEMP). A avaliação destas condições tem sido utilizada para estimar os riscos do desenvolvimento de LEMP nestes pacientes, e abordagens distintas (por vezes extremas) são empregadas para evitar o aparecimento dessa patologia. Atualmente, o grande desafio está em obter um equilíbrio entre os riscos e os benefícios do tratamento com Natalizumabe. Assim, é crucial desenvolver estratégias para monitorar pacientes portadores do vírus JC sob tratamento com Natalizumabe. A título de ilustração, pesquisamos o vírus no sangue e na urina de um paciente sob tratamento durante 12 meses. Também discutimos a eficácia dos métodos atualmente utilizados para avaliação de riscos e as implicações reais de reativação viral.Palavras-chave: esclerose múltipla, Natalizumabe, vírus JC, leucoencefalopatia multifocal progressiva, viruria. Natalizumab (Tysabri), used for treatment of relapsingremitting multiple sclerosis (MS), is a monoclonal antibody directed to the a4b1 integrin, a subunit of an adhesion molecule expressed on the surface of T lymphocytes. The antibodies act by blocking the migration of T Lymphocytes from blood to the CNS through the blood brain barrier (BBB) and attenuate the inflammatory effects 1 . The AFFIRM study showed that monotherapy with Natalizumab (NTZ) for 2 years decreased the relapse rate by 68% and the disability progression rate by 42% compared with placebo 2 . NTZ is well tolerated and the overall incidence of serious adverse events is low. Although the efficacy of NTZ is up to

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Section: Natalizumab and Pmlmentioning

confidence: 99%

Natalizumab treatment for multiple sclerosis: updates and considerations for safer treatment in JCV positive patients

Nali

Moraes

Fink

et al. 2014

Arq. Neuro-Psiquiatr.

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“…Samples were available from 112 patients at the time of PML diagnosis and all tested positive for anti-JCV antibodies [67]. In an ongoing observational study of patients with relapsing MS who were being treated with or considering treatment with natalizumab, the overall anti-JCV antibody prevalence was 56.0% (95% confidence interval 53.0-59.0) at baseline (n = 1096), indicating that a large proportion of patients treated with, or considering, natalizumab are likely to be at risk of PML [72].…”

Section: Natalizumabmentioning

confidence: 99%

Treatment options for patients with multiple sclerosis who have a suboptimal response to interferon‐β therapy

Freedman

2013

Euro J of Neurology

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Background and purpose: Although the first-line disease-modifying therapies (DMTs) interferon beta and glatiramer acetate have a favourable benefit-to-risk profile, they are only partially effective for treating relapsing-remitting multiple sclerosis (RRMS). The optimization of treatment in patients who do not show a maximum response to first-line therapy is critical for achieving the best long-term outcomes. Treatment strategies for patients with a suboptimal response include switching to another first-line DMT or a second-line DMT. Natalizumab and fingolimod are approved for RRMS with high disease activity in the European Union and Canada. Methods: A comprehensive literature search for articles published between 1990 and April 2012 was undertaken.Results: This review discusses key clinical and safety data for fingolimod and natalizumab, particularly in the patient subgroups for whom these treatments are approved. Benefit-to-risk profiles, including first-dose cardiovascular effects associated with fingolimod and the risk of progressive multifocal encephalopathy with natalizumab, are discussed. Conclusion: A descriptive comparison of fingolimod and natalizumab is provided in the context of the decision-making process of how and when to switch patients who have a suboptimal response to first-line therapy.

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“…The overall JCV-positivity rates with this assay have ranged from approximately 50% to 60%. [20][21][22][23] Since this index was introduced, we no longer simply consider a patient's JCV serostatus, but also take into account the magnitude of positivity. Subjects with higher anti-JCV antibody indices are at higher risk of PML than JCV-positive patients with lower indices.…”

Section: Recommendations For Pml Risk Stratification Incorporating Thmentioning

confidence: 99%

“…24 Note that there is a false-negative rate of approximately 2.0% to 2.5% per year, and seroconversion occurs in approximately 2% to 8% of natalizumab-treated patients per year. 20,21 It is also important to note that there can be fluctuation in the JCV index at lower levels. Table 2 shows the panel's recommendations for natalizumab therapy depending on these three risk factors.…”

Section: Recommendations For Pml Risk Stratification Incorporating Thmentioning

confidence: 99%

Use of Natalizumab in Patients with Multiple Sclerosis: 2015 Update

O’Connor

Kremenchutzky

2015

Can. J. Neurol. Sci.

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Anti‐John Cunnigham virus antibody prevalence in multiple sclerosis patients: Baseline results of STRATIFY‐1

Cited by 126 publications

References 21 publications

Natalizumab treatment for multiple sclerosis: updates and considerations for safer treatment in JCV positive patients

Natalizumab treatment for multiple sclerosis: updates and considerations for safer treatment in JCV positive patients

Treatment options for patients with multiple sclerosis who have a suboptimal response to interferon‐β therapy

Use of Natalizumab in Patients with Multiple Sclerosis: 2015 Update

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