ROCKVILLE, Maryland—The US Food and Drug Administration (FDA) has issued a MedWatch alert warning physicians of the first rheumatoid arthritis (RA) patient to develop progressive multifocal leukoencephgalopahy (PML) without prior exposure to a TNFα antagonist (anti-TNF). The agency is warning physicians to consider PML in any rituximab-treated RA patient who develops new neurologic symptoms.

In a letter to healthcare professionals, Genentech Chief Medical Officer Hal Barron, MD, and Biogen rheumatology Chief Medical Officer David Hagerty, MD, advise clinicians treating patients to consult with a neurologist and to consider brain magnetic resonance imaging (MRI) and lumbar puncture to rule out PML. In patients who develop PML, Rituxan should be discontinued.

Two prior fatal cases of PML associated with rituximab RA treatment both involved prior anti-TNF treatment.

According to the companies' letter, the third case of PML occurred in a 73-year old woman with a 3-year history of seronegative RA and prior treatment with leflunomide, hydroxychloroquine, and prednisone. The patient had a history of hypertension, hypothyroidism, osteoporosis, recurrent bronchitis and a cerebrovascular accident.

The patient was treated in February 2009 with one course of Rituxan (1000 mg given two weeks apart) and later developed dysesthesias and ataxia. PML was diagnosed based on clinical symptoms, MRI findings, and detection of JC viral DNA in the cerebrospinal fluid.

According to the companies' letter, “This is the first case of PML in a patient with rheumatoid arthritis treated with Rituxan who has not previously received treatment with a TNF antagonist. PML has been reported in patients with rheumatoid arthritis, including those treated with other immunosuppressive medications in the absence of Rituxan.”

There have been 3 reported cases of PML in approximately 100,000 RA patients receiving Rituxan.

PML is a rare, progressive, untreatable, demyelinating disease of the central nervous system that usually leads to death or severe disability. PML is caused by activation of the JC virus, which is latent in 40-80% of healthy adults.

According to the FDA, “Information to date suggests that patients with RA who receive Rituxan have an increased risk of PML.”