On September 11, the FDA, Genentech and Biogen Idec (the manufacturers of Rituxan) announced that the labeling for the drug is being revised. This comes after the first report that a patient taking Rituxan to treat rheumatoid arthritis had died of the brain infection progressive multifocal leukoencephalopathy (PML). Rituxan is approved to treat RA and non-Hodgkins Lymphoma. Several cases of PML have previously been reported in patients taking Rituxan for unapproved, or off-label, uses, such as treating blood cancer and lupus.
Rituxan controls cancer and rheumatoid arthritis by suppressing the immune system. Rituxan is used in combination with methotrexate to treat adults with RA who have moderate to severe disease and who have not responded to one or more TNF-inhibitors such as Humira or Enbrel. In February 2006, the warning label of Rituxan was updated to include information about the risks of contracting viral infections, including PML.
The actual number of people who have died of PML after being treated with Rituxan is extremely small in relation to the total number of people being treated with the drug. However, the FDA and the manufacturer have urged physicians who were considering treating a patient with Rituxan for any condition to inform the patient of the risk of developing PML and to consider PML in any patient presenting with new onset neurologic symptoms. They recommend that consultation with a neurologist, brain MRI and lumbar puncture as well for patients exhibiting new neurologic symptoms. Finally they stated that Rituxan should be discontinued immediately in patients who develop PML.
Genentech and Biogen Idec said that the female RA patient who died had a complicated case and was being treated for RA, Sjogren's Syndrome and cancer. She had received Rituxan in a long-term safety extension clinical study. In addition, she was treated with a TNF-inhibitor before the study and methotrexate and steroids during and after the study. After the last dose of Rituxan, but 9 months prior to being diagnosed with the JC virus infection, she was underwent chemotherapy treatment for oropharyngeal cancer. She was diagnosed about 18 months after the last dose of Rituxan with a JC virus infection which later resulted in PML and death.
PML causes progressive inflammation of the brain and central nervous system. Patients show neurological symptoms such as confusion, dizziness or loss of balance, difficulty talking or walking, and vision problems. PML is a progressive disease and is usually fatal. There is no treatment or cure for the disease. It is caused by a virus, called the JC virus. The JC virus is commonly acquired during childhood, but remains dormant in the body, so many adults may be infected with the JC virus but never develop PML. The virus stays dormant until a trigger, such as a severely weakened immune system, allows it to become active. PML has been reported in populations such as: HIV-positive patients, immunosuppressed cancer patients, organ transplant patients, and patients with autoimmune disease who were not receiving Rituxan.