Risk Analysis of Natalizumab in Progressive Multifocal Leukoencephalopathy

The panelists look at the treatment of progressive multifocal leukoencephalopathy (PML) and the risks of the medication, natalizumab.

According to Clyde Markowitz, MD, natalizumab was pulled from shelves 3 months after being approved by the US Food and Drug Administration (FDA) in 2004, but it has since returned to the market with more safety precautions in place. Markowitz says the medication has been shown to cause 450 cases of PML and that there is a better understanding now of what causes the condition from a decade ago.

“For one, there’s been a blood test that has become available in the recent past which measures the [John Cunningham (JC)] virus, which is the virus that causes PML,” he says.

Markowitz adds that the duration of treatment with the drug also seems to impact the likelihood of a patient being diagnosed with PML. A third factor, he says, involves prior history of immunosuppressive treatment through drugs like mitoxantrone, azathioprine, and mycophenolate, as he notes that taking those drugs prior to natalizumab increase a patient’s susceptibility to PML 4-fold. Combining all 3 factors, he estimates the odds of a patient having PML at 1 in 80.

Despite the risks, Markowitz says natalizumab is still a beneficial treatment for those who need it, as long as they are closely monitored.

“Patients who go on the medication … seem to be very quiet; their MRIs are quiet and, clinically, they’re quiet,” he notes. “So, we feel fairly comfortable that it is probably one of the most effective treatments we have.”

Patricia Coyle, MD, says it is important for physicians and patients alike to consider the “risk benefit ratio,” as she noted the mortality rate among patients with multiple sclerosis (MS) who also suffer from PML is 23%.

“What the risk stratification allows you to do is really counsel the patient about their risk,” Coyle explains. “For patients who are JC virus antibody negative, their risk of PML is greater than 1 in 10,000, but if natalizumab is an effective treatment, it could be worth the risk for the patients.”