{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T18:06:30Z","timestamp":1776276390574,"version":"3.50.1"},"reference-count":26,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005614","name":"Biogen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005614","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Multiple Sclerosis Journal - Experimental, Translational and Clinical"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:sec><jats:title>Background and objectives<\/jats:title><jats:p> Dimethyl fumarate (DMF), an oral disease-modifying therapy with an established benefit and well-described safety profile, is among the most commonly used therapies for relapsing forms of multiple sclerosis. As of 31 December 2021, &gt;560,000 patients have been treated with DMF, representing &gt;1,190,000 person-years of exposure. Of these, 6413 patients (14,292 person-years) were from clinical trials. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p> Progressive multifocal leukoencephalopathy (PML) has occurred in the setting of lymphopenia (&lt;0.91\u2009\u00d7\u200510<jats:sup>9<\/jats:sup>\/L) in patients treated with DMF. We present detailed clinical characteristics and outcomes of the 12 confirmed PML cases occurring in MS patients on DMF as of 21 July 2021. The PML incidence in DMF-treated patients is 1.07 per 100,000 person-years of DMF exposure. Lymphopenia is the common risk for PML in DMF treatment. <\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p> DMF-related PML is rare but has occurred in the setting of lymphopenia, supporting the current recommendations for absolute lymphocyte count monitoring in all patients, regardless of age and time on therapy. <\/jats:p><\/jats:sec>","DOI":"10.1177\/20552173221132469","type":"journal-article","created":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T04:07:55Z","timestamp":1668139675000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Progressive multifocal leukoencephalopathy outcomes in patients with multiple sclerosis  treated with dimethyl fumarate"],"prefix":"10.1177","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6785-7883","authenticated-orcid":false,"given":"Jennifer","family":"Lyons","sequence":"first","affiliation":[{"name":"Biogen, Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Hughes","sequence":"additional","affiliation":[{"name":"Biogen, Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerry","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Biogen, Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7216-7836","authenticated-orcid":false,"given":"Nicholas","family":"Everage","sequence":"additional","affiliation":[{"name":"Biogen, Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shivani","family":"Kapadia","sequence":"additional","affiliation":[{"name":"Biogen, Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Miller","sequence":"additional","affiliation":[{"name":"Biogen, Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priya","family":"Singhal","sequence":"additional","affiliation":[{"name":"Biogen, Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Smirnakis","sequence":"additional","affiliation":[{"name":"Biogen, Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2022,11,10]]},"reference":[{"key":"bibr1-20552173221132469","doi-asserted-by":"publisher","DOI":"10.1177\/1352458520949158"},{"key":"bibr2-20552173221132469","first-page":"109","volume":"9","author":"Kartau M","year":"2019","journal-title":"Degener Neurol Neuromuscul Dis"},{"key":"bibr3-20552173221132469","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2021.0627"},{"key":"bibr4-20552173221132469","volume-title":"Updated incidence of natalizumab-associated progressive multifocal leukoencephalopathy (PML) and its relationship with natalizumab exposure over time","author":"Giovannoni GKL"},{"key":"bibr5-20552173221132469","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005529"},{"key":"bibr6-20552173221132469","doi-asserted-by":"publisher","DOI":"10.1177\/1756286419836571"},{"key":"bibr7-20552173221132469","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2018.02.028"},{"key":"bibr8-20552173221132469","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1206328"},{"key":"bibr9-20552173221132469","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1114287"},{"key":"bibr10-20552173221132469","doi-asserted-by":"publisher","DOI":"10.1177\/13524585211037909"},{"key":"bibr11-20552173221132469","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2018.10.011"},{"key":"bibr12-20552173221132469","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1415408"},{"key":"bibr13-20552173221132469","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000274"},{"key":"bibr14-20552173221132469","doi-asserted-by":"publisher","DOI":"10.1177\/1352458519852100"},{"key":"bibr15-20552173221132469","volume-title":"Progressive multifocal leukoencephalopathy in a patient treated by dimethyl fumarate for multiple sclerosis with no lymphopenia but exhausted T lymphocyte subpopulations","author":"Garcia JCBH"},{"key":"bibr16-20552173221132469","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-017-8509-9"},{"key":"bibr17-20552173221132469","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002900"},{"key":"bibr18-20552173221132469","volume-title":"Classification of natalizumab case reports with progressive multifocal leukoencephalopathy","author":"Dong-Si TWT"},{"key":"bibr19-20552173221132469","unstructured":"Genentech USA Inc. Ocrevus (ocrelizumab) for US healthcare professionals; additional information on topics of interest, https:\/\/www.ocrelizumabinfo.com\/ocrelizumab-safety-resources.html#additional-information (2022, accessed 24 August 2022)."},{"key":"bibr20-20552173221132469","volume-title":"Cases reported as progressive multifocal leukoencephalopathy in ocrelizumab-treated patients with multiple sclerosis","author":"Clifford DB GA"},{"key":"bibr21-20552173221132469","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30282-X"},{"key":"bibr22-20552173221132469","unstructured":"European Medicines Agency. Tecfidera 120\u2005mg gastro-resistant hard capsules [online], ema.europa.eu\/documents\/product-information\/tecfideraepar-product-information_en.pdf (2021, accessed 13 August 2021)."},{"key":"bibr23-20552173221132469","unstructured":"Biogen Inc. 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