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FDA Drug Safety Podcast for Healthcare Professionals: New risk factor for Progressive Multifocal Leukoencephalopathy (PML) associated with Tysabri (natalizumab)

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Narrator: Welcome to the FDA Drug Safety Podcast for Healthcare Professionals from the Division of Drug Information. Today's Topic: New risk factor for Progressive Multifocal Leukoencephalopathy (PML) associated with Tysabri (natalizumab).

Lindsay Davison, a pharmacist in the Division, will provide you with additional information about this Communication.

Guest Speaker: On January 20, 2012, the Food and Drug Administration issued a Drug Safety Communication informing the public that testing positive for anti-JC virus (JCV) antibodies has been identified as a risk factor for PML. PML is a rare but serious brain infection associated with use of Tysabri for the treatment of multiple sclerosis (MS) or Crohn's disease.

The risks and benefits of continuing treatment with Tysabri should be carefully considered in patients who are found to be anti-JCV antibody positive and have one or more of the other known risk factors for PML. Patients with all three known risk factors have an estimated risk of PML of 11/1,000 users. The risk factors are:

  • The presence of anti-JCV antibodies.
  • Longer duration of Tysabri treatment, especially beyond 2 years.
  • Prior treatment with an immunosuppressant medication, such as mitoxantrone, azathioprine, methotrexate, cyclophosphamide, or mycophenolate mofetil).

The drug label for Tysabri has been revised to reflect this updated information including a table estimating the rate of PML stratified by the three known risk factors.

A patient's anti-JCV antibody status may be determined using an anti-JCV antibody detection test that has been analytically and clinically validated, and has been ordered by a healthcare professional. The Stratify JCV Antibody ELISA test was cleared by FDA on January 20, 2012.Testing positive for anti-JCV antibodies means that a person has been exposed to JCV in the past.

PML is a rare disorder in which the myelin of some brain nerve fibers gets damaged. Although JCV is a common virus that is generally harmless and does not cause symptoms in people whose immune systems function normally, it can cause PML in people with weakened immune systems. Causes of a weakened immune system may include HIV infection, leukemia or lymphoma, or taking a medication such as Tysabri.

The FDA issued two previous Drug Safety Communications on the risk of PML with the use of Tysabri on February 5, 2010 and on April 22, 2011.

At this time, FDA recommends that Healthcare Professionals be aware that:

  • Patients should be informed that PML continues to occur in patients treated with Tysabri.
  • The Tysabri label has been updated with information about a newly identified third risk factor for PML.
  • For purposes of risk assessment, a patient with a positive anti-JCV antibody test at any time is considered to be anti-JCV antibody positive regardless of the results of any prior or subsequent anti-JCV antibody test.
  • Consideration should be given to testing patients prior to treatment or during treatment if antibody status is unknown.
  • Patients who test negative for anti-JCV antibodies are still at risk for the development of PML due to the potential for a new JCV infection or a false negative test result. Consideration should be given to periodic re-testing of patients previously determined to be anti-JCV antibody negative.
  • When assessed, anti-JCV antibody status should be determined using an analytically and clinically validated immunoassay.
  • Patients should be told to contact you, their healthcare professional, if they develop any symptoms suggestive of PML. Symptoms of PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory and orientation, leading to confusion and personality changes. The progression of deficits can lead to death or severe disability over weeks or months.
  • Patients should be monitored and Tysabri should be withheld immediately at the first sign or symptom of PML.
  • Adverse events involving Tysabri should be reported to the FDA MedWatch program at www.fda.gov/medwatch.

Narrator: Thank you for listening. The FDA is committed to keeping healthcare professionals informed of the latest safety information. A link to this communication, including the complete Data Summary, can be found at www.fda.gov/DrugSafetyCommunications. If you have drug questions, you can reach us at druginfo@fda.hhs.gov.

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