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Two patients who were treated with rituximab (Rituxan) for systemic lupus erythematosus developed progressive multifocal leukoencephalopathy (PML), a deadly viral CNS infection, the FDA reported in December.

The FDA issued an alert to make patients and neurologists aware of this serious side effect, and the agency is working with Genentech, the drug's manufacturer, to add warnings about PML to the drug label.

Rituximab is a genetically engineered chimeric murine and human monoclonal antibody directed against the CD20 antigen on the surface of normal and malignant B lymphocytes. It selectively decreases the number of CD20+B lymphocytes, which also increases susceptibility to infection. Marketed since 1997, it is approved only for treating non-Hodgkin lymphoma and rheumatoid arthritis when other treatments fail.

In February 2006, the drug label was updated to include reported cases of PML and other viral illnesses in patients with lymphoma.

Neuroinfectious disease expert Karen L. Roos, MD, recalled that a year ago experts worried about the risk of PML in patients with multiple sclerosis taking natalizumab, a different monoclonal antibody that acts on the immune system. Dr. Roos is a professor of neurology at Indiana University in Indianapolis.

She explained that PML is an infection of the oligodendrocytes by the JC virus, which is acquired in childhood and latently infects the kidneys and bone marrow, and possibly the CNS. Reactivation of the virus produces symptoms of a multifocal leukoencephalopathy: homonymous hemianopia, cognitive abnormalities, and hemiparesis. She told Neurology Today that the “classic neuroimaging abnormalities are a hyperintense lesion or lesions of white matter on T2-weighted imaging and FLAIR MRI with little or no enhancement or mass effect.”

Because there is no effective treatment for PML, survival depends on improving immune function, Dr. Roos said. Increasingly, neurologists who specialize in neuroinfectious diseases care for patients with CNS infections that are reactivated childhood viruses, which result from immunosuppressive and immunomodulator therapies for other diseases, she noted. “Until we have a therapy for PML, I think these drugs should be used only as a last resort for patients whose quality of life is so threatened by their illness, that because of the risk of a fatal infection, it is worth taking.”

Steven Galson, MD, director of the FDA Center for Drug Evaluation and Research, warned in a news release that patients taking rituximab who experience confusion or any major changes in vision, balance, or coordination should seek medical assistance immediately.