Article

Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy

Institute of Neurology, Queen Square, London.
New England Journal of Medicine (Impact Factor: 54.42). 04/2006; 354(9):924-33. DOI: 10.1056/NEJMoa054693
Source: PubMed

ABSTRACT Progressive multifocal leukoencephalopathy (PML) was reported to have developed in three patients treated with natalizumab. We conducted an evaluation to determine whether PML had developed in any other treated patients.
We invited patients who had participated in clinical trials in which they received recent or long-term treatment with natalizumab for multiple sclerosis, Crohn's disease, or rheumatoid arthritis to participate. The clinical history, physical examination, brain magnetic resonance imaging (MRI), and testing of cerebrospinal fluid for JC virus DNA were used by an expert panel to evaluate patients for PML. We estimated the risk of PML in patients who completed at least a clinical examination for PML or had an MRI.
Of 3417 patients who had recently received natalizumab while participating in clinical trials, 3116 (91 percent) who were exposed to a mean of 17.9 monthly doses underwent evaluation for PML. Of these, 44 patients were referred to the expert panel because of clinical findings of possible PML, abnormalities on MRI, or a high plasma viral load of JC virus. No patient had detectable JC virus DNA in the cerebrospinal fluid. PML was ruled out in 43 of the 44 patients, but it could not be ruled out in one patient who had multiple sclerosis and progression of neurologic disease because data on cerebrospinal fluid testing and follow-up MRI were not available. Only the three previously reported cases of PML were confirmed (1.0 per 1000 treated patients; 95 percent confidence interval, 0.2 to 2.8 per 1000).
A detailed review of possible cases of PML in patients exposed to natalizumab found no new cases and suggested a risk of PML of roughly 1 in 1000 patients treated with natalizumab for a mean of 17.9 months. The risk associated with longer treatment is not known.

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    • "Reactivation of JCV occurs usually in immunecompromised or AIDS patients. JCV infection has gained importance to neurologists after the report of two PML cases in multiple sclerosis (MS) patients who received natalizumab [1]. The tremendous advances in the understanding of MS pathology and pharmacotherapy have improved the patients' outcomes significantly. "
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    ABSTRACT: Background. Multiple sclerosis (MS) therapeutics entered a new era after the development of anti-JC virus (anti-JCV) antibody assay that assesses the risk of development of progressive multifocal leukoencephalopathy (PML) in patients treated with natalizumab. Objective. To determine the prevalence of anti-JCV antibody among MS patients in Kuwait. Methods. Using the national MS registry, demographics and disease characteristics of MS patients who were screened for anti-JC virus antibody were collected. The prevalence of anti-JCV antibody seropositivity and its association with demographic and disease characteristics were evaluated. Results. Out of 110 screened MS patients for anti-JCV antibodies, 65.5% were females. Mean age and disease duration were 29.23 ± 8.55 and 5.39 ± 5.04 years, respectively. 47.3% of patients were already on natalizumab and 52.7% of patients were screened for stratification to either natalizumab or a different Disease Modifying Therapy (DMT). The overall prevalence of anti-JC virus antibody was 40%. Gender (P = 0.69), disease duration (P = 0.11), and number of natalizumab infusions (P = 0.64) were not associated with seropositivity. Patients aged ≥30 years were more likely to be seropositive (P = 0.01). Conclusion. The prevalence of anti-JCV antibody is slightly lower than what is reported in published studies. Seropositivity was associated with an increasing age of MS patients.
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    • "There is an evidence that patients may, in exchange for therapeutic benefits, be willing to accept greater levels of risk than are actually posed by some therapies (Calfee, 2006; Johnson et al., 2007a, 2007b). Drug therapies for MS offer a range of potential benefits, but they may also involve lifethreatening risks, including liver failure, leukemia, and progressive multifocal leukoencephalopathy (Brassat et al., 2002; Francis et al., 2003; Yousry et al., 2006). Yet patients may be misinformed particularly by means of internet information, misinterpret the results of scientific research (Jadad et al., 2000; Kaplan and Brennan, 2001), have unrealistic expectations of treatment benefits and harms, and clinicians may be poor judges of a patient′s values (O′Connor et al., 2007). "
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