Progressive Multifocal Leukoencephalopathy (PML)
PML is a rare brain disease caused by infection by, or re-activation of the John Cunningham virus (JC virus). PML can cause severe disability or death. PML is known as an opportunistic infection, which is an infection that is caused by pathogens that usually do not cause illness in people with healthy immune systems. People with weakened immune systems and those with autoimmune diseases such as multiple sclerosis, lupus and rheumatoid arthritis who are treated with certain types of disease-modifying therapies are at higher risk for PML. Disease-modifying therapies alter how the immune system functions, including its ability to effectively fight infections. As a result, people who take these therapies are at higher risk for JC virus infection or re-activation. To date, occurrences of PML have been reported in individuals with MS treated with natalizumab (Tysabri®), dimethyl fumarate (Tecfidera™) and fingolimod (Gilenya®).
Symptoms of PML may include:
· Loss of coordination, clumsiness
· Loss of language ability (aphasia)
· Memory loss
· Vision problems
· Weakness of the legs and arms that gets worse
There is no cure for PML. Treatment includes immediate termination of current medication. In some cases treatment may include treatment with antiretroviral medication or other experimental approaches. Blood plasma exchange may be used to remove any remaining medication from the body for those who have received natalizumab (Tysabri).
In 2005, three cases of PML were reported in patients enrolled in clinical trials for Tysabri. There were two deaths: one in a person with MS who was also taking Avonex, and one in a person with Crohn’s disease who was also taking immunosuppressants. Additional cases of PML were reported in people outside of clinical trials who were not taking another disease-modifying medication at the same time. In total, 134,600 individuals worldwide have received Tysabri and a reported 541 cases of PML (Biogen, 2015).
There are three factors known to increase the risk of PML in people treated with Tysabri: the presence of anti-JCV antibodies (indicates prior infection with JC Virus), longer treatment duration (especially beyond 24 months) and prior treatment with an immunosuppressant, which appear to be independent of Tysabri treatment duration. People who have all three risk factors have the highest risk of PML. The risks and benefits of continuing Tysabri therapy should be carefully considered in these people. Health Canada’s product monograph provides detailed monitoring practices related to PML. For additional information or support with treatment of Biogen ONETM program at 1-855-MSONE-00 or 1-855-676-6300.
Dimethyl fumarate (Tecfidera)
Two cases of PML have been reported in individuals treated with Tecfidera. Both cases exhibited severely reduced blood cell counts – known as lymphopenia, a known adverse effect of this treatment. Health Canada has updated the product monograph for Tecfidera to include monitoring practices for PML. For additional information or support with treatment of Biogen ONETM program at 1-855-MSONE-00 or 1-855-676-6300.
In 2012 a case of PML was reported in a patient who was taking Gilenya, who had
previously been treated with natalizumab (Tysabri). Novartis noted that the PML
was likely associated with previous treatment with Tysabri. In 2015, three cases
of PML were reported in individuals treated with Gilenya who had not been
previously treated with Tysabri.
Novartis has informed regulatory authorities of these cases, and is investigating whether treatment with Gilenya contributed to the development of PML. Novartis has stated that they will continue to explore all potential factors that may contribute to the risk of PML for patients on Gilenya. No changes to patient management or routine monitoring with Gilenya treatment are recommended beyond the guidance in the Gilenya Product Monograph at this time. For additional information or support with treatment of Gilenya please contact Gilenya® Go Program: 1-855-PILL-4MS (1-855-745-5467).