Evaluation of risk management in a natalizumab home infusion procedure
Jean-Christophe LafontaineJulie BoucherJonathan GiovannelliJérôme PetitOlivier OutteryckSara BalagnyHélène Zephir
2
Citation
15
Reference
10
Related Paper
Citation Trend
Keywords:
Natalizumab
In this issue of the Journal, there are reports describing in detail three patients in whom progressive multifocal leukoencephalopathy (PML) developed during treatment with natalizumab, a humanized monoclonal antibody against α4 integrins.13 These patients were among 3000 who had participated in clinical trials of natalizumab for the treatment of multiple sclerosis or Crohn's disease. PML is a deadly opportunistic infection of the central nervous system (CNS) for which there is no specific treatment. It is caused by reactivation of a clinically latent JC polyomavirus infection. This virus infects and destroys oligodendrocytes, leading to multifocal areas of demyelination and . . .
Natalizumab
JC Virus
Slow virus
Demyelinating disease
Cite
Citations (271)
Natalizumab
JC Virus
Cite
Citations (7)
The prior diagnosis of fatal astrocytoma in a 60-year-old man with Crohn's disease treated with natalizumab, a monoclonal antibody against alpha4 integrins, was reclassified as JC virus-related progressive multifocal leukoencephalopathy (PML). Analysis of frozen serum samples showed that JC virus DNA had appeared in the serum three months after the initiation of open-label natalizumab monotherapy and two months before the appearance of symptomatic PML. There was staining of the brain lesion for polyomavirus. This case report, along with two others, suggests that anti-alpha4-integrin therapy can result in JC virus-induced PML.
Natalizumab
JC Virus
Slow virus
Cite
Citations (1,065)
Introduction: Natalizumab is a highly effective monoclonal antibody used for the treatment of multiple sclerosis (MS). It reduces relapses, delays the onset of disease progression and improves disease outcomes in relapsing-remitting MS. However, treatment with natalizumab is associated with progressive multifocal leukoencephalopathy (PML), a severe opportunistic brain infection with John Cunningham virus.
Natalizumab
Relapsing remitting
JC Virus
Cite
Citations (12)
Purpose of review Multiple sclerosis affects many people, often in early adulthood, and causes significant disability. Natalizumab is a novel agent to be evaluated for multiple sclerosis and Crohn's disease that has demonstrated unique efficacy but has unfortunately been implicated in three cases of progressive multifocal leukoencephalopathy. This review covers the mechanism of action of natalizumab and efficacy for multiple sclerosis, the three cases of natalizumab-associated progressive multifocal leukoencephalopathy, our understanding of progressive multifocal leukoencephalopathy, and the mechanisms that may account for these events. Recent findings Natalizumab, an anti-α4-integrin antibody, binds to T-cell surface receptors to prevent migration from the circulation into the brain tissue. Phase II and III trials have been completed and demonstrate previously unseen efficacy in preventing relapses and disease progression. The cases of progressive multifocal leukoencephalopathy, two fatal and one disabling, resulted in the voluntary suspension of natalizumab and bring this entire class of agents into doubt. It is important to determine what led to the development of progressive multifocal leukoencephalopathy in the natalizumab-associated cases and to advance understanding and continue to develop therapies for the treatment of multiple sclerosis. Summary With ongoing safety evaluations, natalizumab is being reevaluated by the US Food and Drug Administration for possible reapproval and return to the market. If natalizumab is reapproved, challenging questions and issues will remain in treating patients with multiple sclerosis.
Natalizumab
Cite
Citations (50)
Natalizumab
JC Virus
Cite
Citations (13)
OBJECTIVE: To evaluate associations of anti-JCV antibody index with PML risk in natalizumab-treated MS patients without prior IS use (no-IS patients), using a recent data set. BACKGROUND: PML risk factors include the presence of anti-JCV antibodies, prior IS use, and duration of natalizumab treatment, especially beyond 2 years. In previous analyses of 71 natalizumab-treated PML patients and 2522 non-PML patients, anti-JCV antibody index differentiated PML risk in anti-JCV antibody positive no-IS patients. DESIGN/METHODS: Analyses involved data from clinical studies and postmarketing sources as of March 2014. Predictive probabilities of having an anti-JCV antibody index above/below a range of thresholds were calculated and used to update PML risk estimates for no-IS patients. RESULTS: Data were available for 101 natalizumab-treated PML patients with serum/plasma samples collected 蠅6 months prior to PML diagnosis and 8112 non-PML anti-JCV antibody-positive patients, including 68 and 6745 no-IS patients, respectively. Anti-JCV antibody index was significantly higher in the 68 PML no-IS patients than in the 6745 non-PML no-IS patients (P<0.0001). For no-IS patients with anti-JCV antibody index at or below thresholds of 0.9 to 1.5, PML risk was approximately 0.1 to 0.2 per 1000 patients during the first 2 years of natalizumab treatment; it ranged from 0.5 to 1.1 and from 0.6 to 1.4 per 1000 patients from month 25 to 48 and from month 49 to 72, respectively. For no-IS patients with index >1.5, PML risk was approximately 1.2 per 1000 patients during the first 2 years of natalizumab treatment, 8.8 per 1000 patients from month 25 to 48, and 10.1 per 1000 patients from month 49 to 72. Longitudinal index data will also be presented. CONCLUSIONS: Consistent with previous findings, this updated analysis suggests the anti-JCV antibody index may differentiate PML risk in anti-JCV antibody positive no prior IS patients. Study Supported by: Biogen Idec
Natalizumab
JC Virus
Slow virus
Cite
Citations (13)
Natalizumab (Tysabri) was the first monoclonal antibody approved for the treatment of relapsing forms of multiple sclerosis (MS). After its initial approval, 3 patients undergoing natalizumab therapy in combination with other immunoregulatory and immunosuppressive agents were diagnosed with progressive multifocal leukoencephalopathy (PML). The agent was later reapproved and its use restricted to monotherapy in patients with relapsing forms of MS. Since reapproval in 2006, additional cases of PML were reported in patients with MS receiving natalizumab monotherapy. Thus, there is currently no convincing evidence that natalizumab-associated PML is restricted to combination therapy with other disease-modifying or immunosuppressive agents. In addition, recent data indicate that risk of PML might increase beyond 24 months of treatment.
Natalizumab
JC Virus
Cite
Citations (112)
Progressive multifocal leukoencephalopathy (PML) is associated with natalizumab treatment. We quantified the risk of PML in patients with multiple sclerosis, according to the presence or absence of three risk factors: positive status with respect to anti–JC virus antibodies, prior use of immunosuppressants, and increasing duration of natalizumab treatment.
Natalizumab
JC Virus
Slow virus
Cite
Citations (1,174)
After a century of futility in the treatment of multiple sclerosis, there is now a deluge of drugs that alter the course of the disease. The half-dozen new oral drugs have excited the most interest, but the monoclonal antibodies, and specifically natalizumab, have a more focused biologic activity and are more potent. It is ironic that natalizumab can cause not just a second neurologic disease, progressive multifocal leukoencephalopathy (PML), but one that, like multiple sclerosis itself, affects the oligodendrocytes and central nervous system myelin.Once it was apparent that PML was related to natalizumab treatment, and the drug was withheld . . .
Natalizumab
Slow virus
Demyelinating disease
Cite
Citations (8)