Rituxan PML Brain Infections Reported in 57 People

A new study indicates that at least 57 patients being treated with the lymphoma-fighting drug Rituxan have developed a rare brain infection, known as progressive multifocal leukoencephalitis (PML), and the cases have involved a 90% fatality rate.

According to the study, published in the medical journal Blood, Rituxan users were more likely to develop PML brain infections than first thought, finding 22 previously unknown cases between 1998 and 2008. However, doctors who contributed to the report say that there is no clear reason why Rituxan PML infections occur, and note that the side effect is still extremely rare in comparison to the drug’s use.

Rituxan (rituximab) is a chimeric monoclonal antibody drug that causes the immune system to target specific types of cells, such as lumphoma cancer cells, to better help the body fight off the disease. It was approved by the FDA in 1997 for treatment of non-Hodgkin’s lymphoma, as well as rheumatoid arthritis. The drug is made by Genentech Inc. and Biogen Idec Inc., with annual sales of about $2.3 billion.

One major concern to doctors who worked on the study was the steady increase in the use of Rituxan to treat “off-label” ailments, such as multiple sclerosis and lupus.

“As use of Rituximab expands to diverse clinical settings, clinicians and patients should be aware of the potential for PML after Rituximab therapy,” the study warns. “Awareness and reporting of Rituximab-associated PML cases to the FDA are essential to improve our understanding of risk factors, natural course, and alternative therapeutic approaches.”

Progressive multifocal leukoencephalitis, also referred to as progressive multifocal leukoencephalopathy or PML, is a rare and often-fatal brain infection caused by a polyomavirus called the JC virus. It involves a progressive inflammation of the central nervous system and the brain, which could cause symptoms such as confusion, blurred vision, speech difficulties, movement problems, dizziness and loss of balance.

Although PML is rare, the brain infection can worsen over time, there is no known cure and it usually results in death.

According to the Rituxan PML study, there was a fatality rate of 100% among those who were diagnosed within three months of their last dose of rituximab and 84% among those who were diagnosed with PML more than three months after the last dose, resulting in an overall Rituxan PML fatality rate of 90%.

Rituxan is one of several drugs that have been linked to PML in recent years. On April 8, 2009, Genentech agreed to issue a phased Raptiva recall, asking physicians to stop prescribing the medication after reports of progressive multifocal leukoencephalitis surfaced. It was determined that the risk of patients developing the fatal brain infection outweighed the benefits provided by the psoriasis medication.

In 2004, Tysabri, an injection used to treat multiple sclerosis and Chron’s Disease, was temporarily recalled by the FDA it was linked to PML. Tysabri was reintroduced in 2006 with more stringent usage guidelines to limit the risk of users developing the brain infection, but at least six new Tysabri PML infections have been reported since the drug’s return.