Natalizumab has demonstrated efficacy in multiple sclerosis (MS), but is associated with increased risk of progressive multifocal leukoencephalopathy (PML), a potentially fatal brain infection caused by the JC virus. At the time of natalizumab's reapproval in 2006, the estimated risk of PML was 1:1,000 (95% confidence interval 0.2-2.80) over 17.9 months of treatment. Since then, 3 risk factors for natalizumab-related PML have emerged:
- Cumulative exposure to natalizumab, with risk increasing up to 3 years, after which risk appears to plateau.
- Previous treatment with cytotoxic or immunosuppressive (IS) drugs
- Prior history of JCV infection, as indicated by the presence of JCV antibodies.
Using a new assay for anti-JCV antibodies ~55% of MS'ers are anti-JCV antibody positive; with false-negative rate of ~2.5% (unfortunately no laboratory assay is perfect).
To date, 28 natalizumab-related PML cases had blood specimens available 1 year or more prior to the development of PML. Using this assay, all 28 patients were JCV seropositive, which is highly statistically significant (p = 3.21 × 10(-8)).
 |
| MRI of someone with PML |
This assay is now clinically available in the United States and Europe.
See Stratify JCV website.
"The negative predictive value of this assay is important. In other words if you are JCV seronegative (negative test) your risk of getting PML is very low. If you are either on natalizumab, or deciding to go onto natalizumab, you may find this information very helpful."
Please see the latest post on this blog about risk stratification:
14 Jan 2012
Please note that if you have been on Natalizumab longer than 24 months, have previously been treated with immunosuppressive drugs, for example mitoxantrone, and you are JC virus positive (blood tests shows you have ...