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Progressive multifocal leukoencephalopathy (PML) is rare viral disease of the brain. Risk of developing the infection has been identified as a potential side effect of treatment with some of the disease modifying drugs, in particular Tysabri (natalizumab). 

PML is caused by a virus called the JC virus, a common infection completely unrelated to MS.  It is normally kept under control by the immune system, causing no problems. If the immune system is weakened and the body is less able to fight an infection, the virus can reactivate and cause serious and potentially fatal inflammation and damage to the brain known as progressive multifocal leukoencephalopathy (PML).

When you are infected with the JC virus you develop antibodies to the virus.  A blood test can detect the presence and level of these antibodies and help give an estimate of your risk of developing PML.  The test indicates your relative level of risk, information which can help you and your MS team make decisions about treatments.

PML and Tysabri

If you are considering taking Tysabri, you will be given this blood test.  If the test is negative it should be repeated throughout treatment with Tysabri as you could become infected at any time.  If a previous blood test found low levels of JC virus infection, you should also continue to have further tests as the virus level may increase. It is recommended that blood tests are repeated every six months.

If the test for JC virus is found to be negative (often referred to as JCV negative) the risk of developing PML is very small (about 0.1 in 1,000, or 1 in 10,000).

A positive test for JC virus (JCV positive) indicates that you are at a higher risk of developing PML, although for most people the risk is still relatively small. This risk also depends on whether you have previously taken a drug that suppresses the immune system (for example, azathioprine, cyclophosphamide, mitoxantrone or methotrexate), how long you have been taking Tysabri (especially over two years) and the amount of JC virus antibody (titre) in your blood.  With different combinations of these factors the risk of developing PML ranges from less than 1 in 1000 up to 12 in 1000.  A guide developed by the MS team at Barts can help you estimate your risk of developing PML. 

Further advice has been published for health professionals concerning monitoring for PML.

As PML damages nerves, some of its symptoms are similar to those of MS, such as weakness, visual problems, impaired speech and cognitive problems. If you start taking Tysabri you will be informed of the early signs and symptoms of PML and advised to report any new or worsening symptoms.  If PML is suspected at any point during treatment, the drug will be discontinued immediately and further tests carried.

PML is treated with plasma exchange which involves a series of blood transfusions to flush Tysabri from the body and allow the immune system to fight the JC virus infection.

PML and Gilenya

Three cases of PML have been reported in people taking Gilenya (fingolimod). The risk of developing PML on Gilenya is considered very low but if you are worried, discuss your concerns with your MS team.

Before you start taking Gilenya, it is important that you have had a recent (within 3 months) MRI scan. When you start treatment, you should be informed of the early signs and symptoms of PML. These can be similar to an MS relapse, so it is important to report any new or worsening symptoms. If PML is suspected during treatment, an MRI scan should be performed and Gilenya suspended until PML has been excluded.

Further advice has been published for health professionals concerning monitoring for PML.

PML and Tecfidera

Three cases of PML have been reported in people taking Tecfidera (dimethyl fumarate). The risk of developing PML on Tecfidera is considered very low but if you are worried, discuss your concerns with your MS team.

Before you start taking Tecfidera, it is important that you have had a recent (within 3 months) MRI scan. When you start treatment, you should be informed of the early signs and symptoms of PML. These can be similar to an MS relapse, so it is important to report any new or worsening symptoms. If PML is suspected during treatment, an MRI scan should be performed and Tecfidera suspended until PML has been excluded. The cases of PML have occurred in people who have had very low levels of lymphocytes (a type of white blood cell) for an extended period of time. Once you've started treatment you should have blood tests every three months to monitor your blood cell counts.

Further advice has been published for health professionals concerning monitoring for PML.

References

  • Bloomgren G, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. New England Journal of Medicine 2012; 366:1870-1880. Full article
  • Sørensen PS, et al. Risk stratification for progressive multifocal leukoencephalopathy in patients treated with natalizumab. Multiple Sclerosis 2012;18(2):143-152. Summary

Last updated: 7 December 2016
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