Multiple Sclerosis Drug Natalizumab Linked to High Levels of John Cunningham Virus

Patients taking natalizumab may be more susceptible to John Cunningham virus-related problems, potentially increasing their risk for developing progressive multifocal leukoencephalopathy.

The multiple sclerosis (MS) drug natalizumab may increase a patient’s risk for developing a virus risk biomarker — which is often fatal, according to findings published online in the journal Neurology Neuroimmunology and Neuroinflammation.

Researchers from the University of Chicago explained in a press release that a sign of the often-fatal disease called progressive multifocal leukoencephalopathy (PML) is damage to the brain’s white matter. John Cunningham virus (JCV), which is controlled by the body’s immune system, causes PML. But patients taking natalizumab have compromised immune systems because the immune cells are prevented from getting into the brain, leaving MS patients more susceptible to JCV-related problems.

The researchers tested the blood of 525 MS patients throughout a 15-month period in Germany and 711 additional MS patients in France over a two-year period. All of the patients were taking natalizumab.

Ten percent of the German group and 9% of the French group changed over from being anti-JCV-negative to anti-JCV-positive, annually. The general population, as well as MS patients not taking natalizumab, typically changes over at a rate of about 1% per year. Of the 399 patients in the German group who were anti-JCV-negative, 43 patients tested positive for the antibodies during the studies. Of the 243 anti-JCV patients at baseline, 41 tested positive for the antibodies during the duration of their studies.

“It is important that people with MS taking natalizumab speak with their doctor before making any changes to their treatment,” senior study author Heinz Wiendl, MD explained in the statement. “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 MS.”

The anti-JCV-positive patients from baseline demonstrated increased antibody levels over time — natalizumab treated patients had a 13% annual boost in their level of anti JCV antibodies. In the German group, the researchers noted the “medium risk” patients group increased by 7 people, or an increase from 5% to 6% in 15 months. In the French group, the increase was from 22% to 25% in the two-year period.

“Even though anti-JCV antibodies were present at a higher level, it does not necessarily mean that an individual will get PML,” corresponding editorial author Adil Javed, MD, PhD, wrote. “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.”