Tysabri Brain Infection Risk Increases with Number of Infusions: FDA

The FDA has issued another warning about the risk of brain infections from Tysabri, indicating that the more infusions a patient receives of the multiple sclerosis drug, the higher their risk of contracting progressive mutifocal luekoencephalopathy (PML), a rare and often fatal infection in the brain.

Healthcare professionals were notified on Friday about this new safety information and label changes about the risk of Tysabri brain infections. The new warnings come after the agency confirmed at 31 cases of PML brain infectiions among Tysabri users.

Tysabri (natalizumab) is an intravenous injection given every 28 days to treat 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. Sales of Tysabri bring in about $1 billion annually.

A Tysabri recall was issued in 2005 after three users developed the rare and life-threatening brain infection, which attacks the central nervous system, damaging and inflaming the white matter areas of the brain. The drug was reintroduced in July 2006 with stronger warnings about the potential PML brain infection side effects of Tysabri and it was only made available under strict usage guidelines.

PML is believed to be caused by the common JC virus, and side effects of Tysabri may reduce the ability of the immune system to combat the virus.

Symptoms of PML brain infections from Tysabri could include confusion, blurred vision, speech and movement difficulties, dizziness and loss of balance. In most cases, PML has a very high fatality rate, however, some Tysabri users have had a better prognosis due to early detection and the use of a plasmapharesis treatment, which removes Tysabri from the system rapidly and allows the immune system to fight off the virus.

Due to the risks of PML, Tysabri is only available in the U.S. after its re-release through a joint FDA and BioGen risk reduction program called Tysabri Outreach Unified Commitment to Health (TOUCH). The TOUCH program monitors each patient for signs of PML or other opportunistic viruses that may strike at patients with lowered immune systems.

By studying the 31 cases of PML since Tysabri was re-introduced, the FDA has determined that there have been no reports of PML in patients treated for less than 12 months. Patients who have had 24 to 36 infusions in the U.S. have developed PML at a rate of 1 in 1,000. Outside of the U.S., the rate is 1 in 2,000, but the FDA does not know why there is a discrepancy.

The FDA recommends that doctors take the patient off Tysabri at the first signs of PML.

The safety warning also contained information about another Tysabri side effect known as Immune Reconstitution Inflammatory Syndrome (IRIS). The condition is rare, causing an inflammatory response in patients who recovered from PML after being taken off Tysabri infusions. IRIS can cause an unexpected decline in their condition. It has not been detected in patients who discontinued Tysabri for other reasons.