FDA Drug Safety Communication: Tysabri

Multiple sclerosis and Crohn's disease treatment may cause risk or rare but serious brain infection

/ Author:  / Reviewed by: Joseph V. Madia, MD

The U.S. Food and Drug Administration (FDA) continues to evaluate the risk of progressive multifocal leukoencephalopathy (PML), a rare but serious brain infection, associated with use of Tysabri" data-scaytid="7">Tysabri (natalizumab" data-scaytid="9">natalizumab) for the treatment of multiple sclerosis (MS) and Crohn's disease.

The FDA has updated the Tysabri label to give new information about the size of this risk, as well as to include new safety information about patients who have taken other drugs that suppress the immune system, who may be at a higher risk for PML.

The revised drug label includes:

  • A table summarizing rates of PML with Tysabri use according to the number of infusions (how long the drug is taken or duration of exposure).
  • Information on a newly identified PML risk factor. Patients who took an immune system suppressing medication (e.g., mitoxantrone" data-scaytid="37">mitoxantrone, azathioprine" data-scaytid="39">azathioprine, methotrexate, cyclophosphamide" data-scaytid="43">cyclophosphamide, mycophenolate) prior to taking Tysabri have been shown to be at an increased risk for developing PML. The Tysabri label already warned that using immune system suppressing medications at the same time as Tysabri may increase the risk of developing PML.

Facts about Tysabri (natalizumab)

  • Tysabri (natalizumab) is in a class of medications called immunomodulators. It works by stopping certain cells of the immune system from causing damage to the body.
  • Tysabri has been approved by the FDA for the treatment of relapsing forms of multiple sclerosis since November 2004 and for the treatment of moderately to severely active Crohn's disease since January 2008.

 The FDA anticipates that the new PML information in the label will aid healthcare professionals in assessing the risk for PML and in discussing that risk with their patients. The Tysabri label will be updated periodically as new information about the risk for PML becomes available.

Based on the available information to date, the FDA continues to believe that the benefits of taking Tysabri outweigh the potential risks. Tysabri will continue to be available to patients only through a restricted distribution program called the Tysabri Outreach Unified Commitment to Health (the TOUCH Prescribing Program).

The FDA issued a previous Drug Safety Communication (DSC) on the risk of PML with the use of Tysabri on February 5, 2010.

Additional Information for Patients

  • Tysabri continues to be associated with PML.
  • The risk of developing this disease increases with the number of Tysabri infusions received.
  • The risk of developing PML also increases if you have taken a medication that suppresses the immune system (called an immunosuppressant) in the past. Tell your healthcare professional if you have previously taken an immunosuppressant medication. Examples of immunosuppressants are mitoxantrone, azathioprine, methotrexate, cyclophosphamide, and mycophenolate.
  • Discuss any questions or concerns about Tysabri and the risk of PML with your healthcare professional.

Data Summary

102 cases of PML have been reported among 82,732 patients treated with Tysabri worldwide through February 28, 2011.

New data show that the risk of developing PML is increased in patients who have been treated with immunosuppressants in the past, prior to receiving Tysabri. The effects of prior treatment with immunomodulators (e.g., beta-interferons, glatiramer acetate) or of prior, short-term treatment with corticosteroids for MS flares on the risk of PML in Tysabri-treated patients have not been evaluated. The Tysabri label already warned that concurrent use of immunosuppressant drugs with Tysabri may increase the risk of developing PML over the risk observed with use of Tysabri alone.

Data from the past year have confirmed that the risk of developing PML is greater in patients who have received more than 24 Tysabri infusions (corresponding to two years of continuous treatment) compared to patients who have received fewer than 24 infusions.

The Tysabri label has been updated with a table to show the risk of PML for discrete treatment intervals (durations of exposure). This PML risk table contains a date to reflect when the data were current, and will be updated periodically.