Tysabri PML Infection Risk Increases With Long-Term Use: Study

Biogen researchers indicate that side effects of Tysabri appear to increase the risk of a potentially lethal brain infection, known as progressive multifocal leukeoencephalopathy (PML), the longer individuals stay on the multiple sclerosis drug. 

In a study published last month in the medical journal The Lancet Neurology, researchers noted that the Tysibri PML infection risk increased over time, and was also higher among patients who had previous immunosuppressant use.

Progressive multifocal leukeoencephalopathy (PML) is a rare and deadly brain infection that has been linked to several different immunosuppressant drugs, including Tysabri. It is believed to occur when the drug disables the immune system enough for the JC virus, a strain of paopvavirus, to take hold. Estimates indicate that about 50% to 60% of the population has contracted the JC virus.

Tysabri (natalizumab, also known as NTZ) is an intravenous injection given every 28 days to treat multiple sclerosis (MS) and Crohn’s disease. Manufactured by Biogen Idec Inc. and marketed with Elan Corp PLC, Tysabri has been shown to prevent relapse, cognitive decline and vision loss associated with MS.

Shortly after the drug was introduced in 2004, a Tysabri recall was issued after cases of PML were identified, including several deaths. The medication was re-introduced in 2006, with stricter guidelines for usage and more prominent warnings about the possible link between Tysabri and PML.

In the latest study, researchers at Biogen looked at data on more than 37,000 patients pooled from four large observational studies. They looked at annual PML risks for patients with and without previous immunosuppressant use by checking for the anti-JCV antibodies.

According to the findings, 156 of the patients developed PML. They deduced that the PML probability over six years, or 72 Tysabri infusions was 2.7% in patients with previous immunosuppressant use, and only 1.7% in those without. The patients at highest risk of PML went from an annual risk of 0.2 cases per 1,000 person-years in the first year to 10 cases per 1,000 person years by year six of Tysabri use.

“Consistent with previous natalizumab-associated PML risk estimates, this analysis showed that the risk increases with previous immunosuppressant exposure and longer natalizumab treatment,” the researchers concluded. “As a result of our analyses, regulatory labelling of natalizumab in the European Union as well as in other regulatory jurisdictions throughout the world has been updated to include these new PML risk estimates.”

Hundreds of cases of PML have been linked to Tysabri, and many of those patients have died.