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Progressive multifocal leukoencephalopathy
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===Multiple sclerosis medications=== [[Natalizumab]] (Tysabri) was approved in 2004 by the FDA for the treatment of multiple sclerosis (MS). It supposedly works by preventing white blood cells from entering the brain. It was subsequently [[list of withdrawn drugs|withdrawn from the market]] by its manufacturer after it was linked with three cases of PML.<ref name="pmid21777829">{{cite journal|title=Natalizumab treatment for multiple sclerosis: updated recommendations for patient selection and monitoring|journal=Lancet Neurology|date=August 2011|volume=10|issue=8|pages=745–58|doi=10.1016/S1474-4422(11)70149-1|pmid=21777829|last1=Kappos|first1=Ludwig|last2=Bates|first2=David|last3=Edan|first3=Gilles|last4=Eraksoy|first4=Mefkûre|last5=Garcia-Merino|first5=Antonio|last6=Grigoriadis|first6=Nikolaos|last7=Hartung|first7=Hans-Peter|last8=Havrdová|first8=Eva|last9=Hillert|first9=Jan|last10=Hohlfeld|first10=Reinhard|last11=Kremenchutzky|first11=Marcelo|last12=Lyon-Caen|first12=Olivier|last13=Miller|first13=Ariel|last14=Pozzilli|first14=Carlo|last15=Ravnborg|first15=Mads|last16=Saida|first16=Takahiko|last17=Sindic|first17=Christian|last18=Vass|first18=Karl|last19=Clifford|first19=David B|last20=Hauser|first20=Stephen|last21=Major|first21=Eugene O|last22=O'Connor|first22=Paul W|last23=Weiner|first23=Howard L|last24=Clanet|first24=Michel|last25=Gold|first25=Ralf|last26=Hirsch|first26=Hans H|last27=Radü|first27=Ernst-Wilhelm|last28=Sørensen|first28=Per Soelberg|last29=King|first29=John|s2cid=15639613|hdl=2078.1/124907}}</ref> All three initial cases were taking natalizumab in combination with [[interferon beta-1a]].<ref name="pmid21777829"/> After a safety review, the drug was returned to the market in 2006 as a monotherapy for MS under a special prescription program.<ref name="pmid21777829"/> As of May 2011, over 130 cases of PML had been reported in MS patients, all in patients who had taken natalizumab for more than a year.<ref name="pmid21777829"/> While none of them had taken the drug in combination with other disease-modifying treatments, previous use of MS treatments increases the risk of PML between three- and four-fold.<ref name="pmid21777829"/> The estimated [[prevalence]] of PML in MS is 1.5 cases per thousand natalizumab users.<ref name="pmid21777829"/> Around 20% of MS patients with PML die, and most of the rest are very disabled.<ref name="pmid21777829"/> One case study describes an MS patient who, during a 4-year course of [[dimethyl fumarate]], developed PML and died.<ref>{{Cite web | url=https://www.gov.uk/drug-safety-update/dimethyl-fumarate-tecfidera-fatal-pml-in-a-ms-patient-with-severe-prolonged-lymphopenia | title=Dimethyl fumarate (Tecfidera): Fatal PML in an MS patient with severe, prolonged lymphopenia}}</ref> [[Fingolimod]] (Gilenya) was [https://www.drugs.com/history/gilenya.html approved in 2010] by the FDA for MS. In 2015, the first case of PML and a case of "probable PML" were reported by two Gilenya users that could not be tied to previous immunosuppressant therapies. These new cases are now being added to the drug information sheet included with every prescription (i.e. the "drug label").<ref>{{cite web |title=FDA Drug Safety Communication: FDA warns about cases of rare brain infection with MS drug Gilenya (fingolimod) in two patients with no prior exposure to immunosuppressant drugs |url=https://www.fda.gov/Drugs/DrugSafety/ucm456919.htm |website=US Food and Drug Administration |access-date=31 December 2018}}</ref>
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