Medicinal Products

Direct healthcare professional communication on updates to PML risk minimisation measures for Tysabri (natalizumab)


Biogen Idec Limited, in agreement with the Agency for Medicinal Products and Medical Devices of Croatia (HALMED) and the European Medicines Agency (EMA), informs healthcare professionals of important new measures that may aid in earlier identification of progressive multifocal leukoencephalopathy (PML) in patients receiving Tysabri. The letter reminds healthcare professionals of the key measures to minimise the risk of PML.


  • Recent analyses suggest that early detection of PML is associated with improved outcomes. PML which is clinically asymptomatic at diagnosis can represent unilobar disease on magnetic resonance imaging (MRI) more often than symptomatic PML, with a higher survival rate and better clinical outcome.
  • More frequent MRIs (e.g. every 3-6 months) using an abbreviated MRI protocol (FLAIR, T2-weighted and DW imaging) should be considered for patients at higher risk of PML.
  • In patients who have not received prior immunosuppressant therapy and are anti-JCV antibody positive, the level of anti-JCV antibody response (index) is associated with the level of risk for PML. Current evidence suggests that the risk of PML is low at index value ≤0.9, and increases substantially at values above 1.5 in patients who have been on treatment with Tysabri for longer than 2 years.
  • Patients at higher risk of PML include those who are anti-JV antibody positive, have received more than 2 years of Tysabri therapy and have received prior immunosuppressant therapy or have high anti-JCV antibody response (index), have received more than 2 years of TYSABRI therapy and have no prior history of immunosuppressant therapy.
  • Patients with low anti-JCV antibody index values and no history of prior immunosuppressant use should be retested every 6 months once they reach the 2-year treatment point.

Further information

Tysabri is a medicine used to treat adults with highly active multiple sclerosis (MS), a disease of the nerves in which inflammation destroys the protective sheath surrounding the nerve cells. Tysabri is used in the type of MS known as ‘relapsing-remitting’ MS, when the patient has attacks (relapses) in between periods with no symptoms (remissions). It is used when the disease has failed to respond to treatment with a beta interferon or glatiramer acetate (other types of medicines used in MS), or is severe and getting worse rapidly.

The letter provides healthcare professionals with additional information related to this safety issue, updated estimates of the risk of PML in patients treated with Tysabri as well as summary of recommendations.

Further detailed recommendations will be included in educational material that is currently in preparation and will be distributed separately.

Here you may view the direct healthcare professional communication.

Healthcare professionals are reminded that they should report any adverse reaction, as well as quality defect to HALMED. Patients who have developed any adverse reaction to medicinal product may report it directly to HALMED. HALMED recommends patients to contact their doctor or pharmacist regarding any adverse reaction they notice.