A study found 57 patients who took Rituxan became ill with PML, a fatal brain disease, and 93 per cent of them died within two months.
A 39-year-old Texan with chronic leukemia suddenly began mixing up his words. Next, he stumbled over basic math equations, and had trouble reading.
A biopsy revealed he had a brain infection called progressive multifocal leukoencephalitis (PML) which attacks the brain's white matter, eating away at it.
A 57-year-old New York lawyer with lymphoma had a similar experience. One day he was completing a crossword puzzle from The New York Times. The following day he couldn't think of the words to fill the squares.
Both patients had just been put on Rituxan - a widely used cancer drug also known as rituximab, taken by at least one million people all over the world. Both men were dead within two months.
They are two of 57 patients on the drug who became ill with PML, reported in a new study by Charles Bennett, a hematologist and oncologist at Northwestern University Feinberg School of Medicine in Chicago. In 93 per cent of the cases, which took place from 1998 to 2008 in the United States and Europe, the patients died within two months of being diagnosed with PML. The study was published in a recent issue of Blood, a scholarly, peer-reviewed journal.
It is not yet known how the medication is linked to the unusual brain infection, or why certain patients may be more at risk. But the issue raises grave concerns for Dr. Bennett, who specializes in drug safety issues and runs RADAR (Research on Adverse Drug Events and Reports).
"We don't want to take the drug off the market. It is a home run for people who have lymphoma," he said in an interview. "But we want to make sure we can identify which patients are at higher risk, and not give them the drug, and ensure that doctors and patients are well-educated about the side affects."
Rituxan, which is on the market in Canada and the U.S, is used principally for patients with non-Hodgkin's lymphoma. However, some doctors also prescribe it for other illnesses, including lupus, anemia, multiple sclerosis and rheumatoid arthritis. These diseases are chronic and patients may live a long time, making the calculation of the risk-benefit ratio different than it is for cancer patients.
Genentech, the drug's manufacturer, said in an interview that it monitors Rituxan's safety, and reports any adverse events to the U.S. Federal Drug Administration.
"The potential contribution of Rituxan to the development of PML is unknown," said spokesperson Amy Berry. "However, it cannot be excluded."
Last year, Genentech issued a warning to doctors alerting them that a patient with rheumatoid arthritis who had been taking the drug died from PML. In 2006, two patients with lupus also developed the illness after taking the drug.
Genentech, though, is keen to expand its usage, and has applied to the FDA to have Rituxan approved for chronic lymphocytic leukemia, a disease which progresses slowly.
Health Canada warns on its website that the safety and efficacy of Rituxan to treat autoimmune diseases hasn't been established- with the exception of rheumatoid arthritis.
Two other similar drugs in this new class of medications, known as monoclonal antibodies, have been taken off the market because of the PML risk. Raptiva was removed from store shelves in the U.S. and Europe last year, though is still available Canada, and Tysabri was removed in the U.S. for 18 months from 2005 to 2006.
Dr. Bennett became a "pharmacovigilante" in 1998, after a friend nearly died from a drug's side effect. As head of RADAR, he works with physicians from all over the world, working to save the lives of the estimated 100,000 people in the U.S. alone who die from adverse drug reactions. RADAR's research has resulted in warnings on billion-dollar drugs, such as Plavix.
The link between Rituxan and brain infection first came to Dr. Bennett's attention when an 83-year-old Chicago woman at the hospital where he works began parroting the same phrases over and over again. When her doctor asked her how she was, she replied: "I am fine. I am fine. I am fine."
A brain biopsy showed PML. Concerned, Dr. Bennett looked for similar cases and found 56 more, by pouring over FDA records and medical literature, and contacting 12 major cancer centres in the U.S.
"I bought a plane ticket and flew to New York and other cities, and talked doctor-to-doctor. That opened a lot of different doors," he said, of his efforts to track the cases.
PML, a fatal disease of the central nervous system, is difficult to diagnose because the symptoms - a sudden difficulty in thinking, walking, or speaking, forgetfulness and even paralysis - resemble those of early dementia.
The virus is found in up to 80 per cent of healthy adults, but only turns into an infection in people with severe immune deficiency, such as those living with HIV or cancer.
Before the study, doctors had been reticent to report patients who developed PML to the FDA. "This is typical, because there is a lot of paper work involved and it is a lot of work," said Dr. Bennett. "Only 1 per cent of adverse reactions to drugs ever get reported to the FDA. We need to do a better job."