Natalizumab tied to rising John Cunningham virus levels in people with multiple sclerosis


People taking natalizumab for the treatment of multiple sclerosis may be at a heightened risk of developing of progressive multifocal leukoencephalopathy (PML).

A study published online by Neurology Neuroimmunology and Neuroinflammation has found that people taking natalizumab for multiple sclerosis have up to a 10 times greater risk of developing PML, the risk biomarker for activity of the John Cunningham virus (JCV).

“An increase in the levels of anti-JCV antibodies could signify an increased risk of PML,” says study senior author Heinz Wiendl of the University of Muenster, Germany, and member of the American Academy of Neurology. The level of antibodies is a marker for exposure to JCV and therefore the risk for PML.

In the study, researchers used a blood test to monitor levels of anti-JCV antibodies over a 15-month period in 525 people in Germany and over two years in 711 people in France. All had multiple sclerosis and were taking natalizumab.

They found people converted from being anti-JCV negative to anti-JCV positive at the following annual rates: 10% in the German group and nearly 9% in the French group. Those rates are much higher than the rate of 1% per year for the general population and for people with multiple sclerosis not treated with natalizumab. In the German group, 43 of 339 people who were initially anti-JCV negative tested positive for the antibodies during the study. In the French group, 41 of 243 people who were anti-JCV negative tested positive for the antibodies during the study. 

In people who were anti-JCV positive already at the beginning of the study, their level of antibodies also rose over time. Treatment with natalizumab was associated with a 13% yearly rise in the level of anti-JCV antibodies in the blood. In the German group of 525 people, those considered medium risk of PML grew by seven people, representing 5% of the group at the beginning of 15 months, increasing to 6%. The high-risk group grew by 14 patients, initially representing 22% of the group, increasing to 25%.

“Even though anti-JCV antibodies were present at a higher level, it does not necessarily mean that an individual will get PML,” says Adil Javed of the University of Chicago, USA, who wrote a corresponding editorial, and is a member of the American Academy of Neurology. “The risk of PML in JCV positive people being treated for multiple sclerosis with natalizumab without prior immunosuppressant therapy is one in 1,000 people. The risk of a multiple sclerosis attack in untreated patients is one in every two people.”

Wiendl says, “It is important that people with multiple sclerosis taking natalizumab speak with their doctor before making any changes to their treatment. Still, this study shows anti-JCV antibodies may serve as a useful biomarker. Natalizumab did appear to increase the levels of anti-JCV antibodies and this higher level may be associated with a higher risk of PML. The results of this study underscore the need for frequent monitoring of anti-JCV antibodies in people who are being treated with natalizumab for multiple sclerosis.”

Wiendl noted that the study does not prove that natalizumab causes the virus to replicate at higher rates, leading to higher anti-JCV antibody levels, but that it shows an association.

The study was supported by the German Research Foundation, the PML Consortium, the Competence Network for Multiple Sclerosis, the French Ministry of Health, the French MS Society and the European Union.