Rituxan Patients and Multifocal Leukoencephalopathy

Rheumatoid Arthritis Patient in Rituxan Study Developed Fatal Case of PML

A fatal case of PML (progressive multifocal leukoencephalopathy) has been identified in a rheumatoid arthritis (RA) patient who participated in a safety extension clinical trial for Rituxan (rituximab). Consequently, the FDA and the drug's manufacturer has issued a warning and will update Rituxan prescribing information to include PML.

What Is PML?

PML is also known as progressive multifocal leukoencephalopathy.

According to the National Institute of Neurological Disorders and Stroke, "Progressive multifocal leukoencephalopathy (PML) is caused by the reactivation of a common virus in the central nervous system of immune-compromised individuals. Polyomavirus JC (often called JC virus) is carried by a majority of people and is harmless except among those with lowered immune defenses."

Is More Known About the RA Patient Who Developed PML?

The RA patient had first developed a JC virus infection and then PML. Death from PML occurred 18 months after the patient had received the last dose of Rituxan in the safety extension study.

The RA patient also had developed oropharyngeal cancer (throat cancer) and was treated with chemotherapy and radiation 9 months before developing PML. The patient had a somewhat complicated medical history that could have contributed to the development of PML. Aside from RA, the patient had Sjogren's syndrome and undetectable complement C4 levels.

The patient was treated with methotrexate, steroids, and a TNF blocker prior to being treated with Rituxan. Methotrexate and steroids were also used during and after rituximab treatment.

What Is the FDA Doing in Response to the PML Case?

The FDA is revising prescribing instructions and informing healthcare professionals in a letter and the public on its website about the fatal case of PML.

What Should RA Patients Treated With Rituxan Do?

As always, discuss your concerns with your doctor. Experts are advising that if a patient treated with Rituxan develops neurologic symptoms -- a consultation with a neurologist, brain MRI, and lumbar puncture should be considered. Patients who develop PML should discontinue Rituxan, possibly discontinue or reduce other immunosuppressants, while considering anti-viral therapy. But, there really is no treatment that can resolve PML if it develops.


FDA: Fatal Case of Progressive Multifocal Leukoencephalopathy in Patient Receiving Rituximab. Doctor's Guide News. September 11, 2008.

FDA Medwatch. Important New Safety Information Regarding Progressive Multifocal Leukoencephalopathy With Use of Rituxan. September 11, 2008.

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