Rituximab and Progressive Multifocal Leukoencephalopathy (PML)

Should Rheumatoid Arthritis Patients Be Concerned?

People with rheumatoid arthritis who take Rituxan (rituximab) for their symptoms should be aware of the drug's association with progressive multifocal leukoencephalopathy (PML), a rare and often fatal disease of the central nervous system.

While the number of cases is very low, some rituximab patients have developed PML. As a result, the U.S. Food and Drug Administration (FDA) and the drug's manufacturer have issued a warning about the association.

If you are on or considering starting Rituxan, educate yourself about the potential risks.

Rituximab Use for Rheumatoid Arthritis

Rituximab is an intravenous biologic drug known as a monoclonal antibody that was initially approved by the FDA for treatment of non-Hodgkin's lymphoma. It has subsequently been approved for treatment of rheumatoid arthritis.

This drug helps calm the overactive immune response that leads to inflammation in the body and joints. In RA, it can be used in combination of other biologics or corticosteroids when other treatments are ineffective.

The majority of RA patients who use rituximab have no problems. Researchers are not certain why a small percentage of RA patients using rituximab develop PML. There are no related cofactors to developing PML, such as age, dose, and duration of treatment.

Developing PML

According to the National Institute of Neurological Disorders and Stroke, progressive multifocal leukoencephalopathy is "a disease of the white matter of the brain caused by a virus infection that targets cells that make myelin—the material that insulates nerve cells (neurons)."

The virus in question is polyomavirus JC (often called the John Cunningham or JC virus) and is carried by a majority of people. It's generally harmless except among those with lowered immune defenses.

In those who develop PML, the virus infects multiple areas of the brain, damaging it as the infection rapidly worsens and causing lasting consequences—not uncommonly, death.

PML is well-documented in oncology, particularly in non-Hodgkin lymphoma and chronic lymphocytic leukemia patients. However, unlike RA, PML is a known risk factor in those diseases.

FDA Warning About PML Risk

While cases of PML associated with rituximab have been documented, the infection rate is very low.

One study measured the frequency of PML cases in people who received rituximab and the rate was only 2.56 per 100,000 RA patients.

Despite the low risk, the FDA issued a black box warning for rituximab in relation to rheumatoid arthritis patients.

It informs physicians of the following:

"Fatal infusion reactions within 24 hours of Rituxan infusion occur; approximately 80% of fatal reactions occurred with first infusion. Monitor patients and discontinue Rituxan infusion for severe reactions."

Patients who develop PML should, under the guidance of a physician, discontinue Rituxan and possibly discontinue or reduce other immunosuppressants while considering anti-viral therapy. However, there is no treatment that can resolve PML if it develops.

A Word From Verywell

If your doctor recommends rituximab for your RA, discuss any concerns you have. The risks are very low and are generally outweighed by the benefits, but it's important that you always feel confident about any drug you are taking.

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  1. Berger JR, Malik V, Lacey S, Brunetta P, Lehane PB. Progressive multifocal leukoencephalopathy in rituximab-treated rheumatic diseases: a rare event [published correction appears in J Neurovirol. 2018 Apr 10;:]. J Neurovirol. 2018;24(3):323–331. doi:10.1007/s13365-018-0615-7

  2. National Institute of Neurological Disorders and Stroke. Progressive multifocal leukoencephalopathy information page. Updated July 29, 2019.

  3. US Food and Drug Administration. Boxed warning, Rituxan.