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Their role in progressive multiple sclerosis, where there is a particularly urgent need for improved biomarkers, is less clear. The objectives of this systematic review are to summarise the literature on neurofilament light and heavy in progressive multiple sclerosis, addressing key questions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A systematic search of PubMed, Embase, Web of Science and Scopus identified 355 potential sources. 76 relevant sources were qualitatively reviewed using QUADAS-2 criteria, and 17 were identified as at low risk of bias. We summarise the findings from all relevant sources, and separately from the 17 high-quality studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Differences in neurofilament light between relapsing\u2013remitting and progressive multiple sclerosis appear to be explained by differences in covariates. Neurofilament light is consistently associated with current inflammatory activity and future brain atrophy in progressive multiple sclerosis, and is consistently shown to be a marker of treatment response with immunosuppressive disease-modifying therapies. Associations with current or future disability are inconsistent, and there is no evidence of NFL being a responsive marker of purportedly neuroprotective treatments. Evidence on neurofilament heavy is more limited and inconsistent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Neurofilament light has shown consistent utility as a biomarker of neuroinflammation, future brain atrophy and immunosuppressive treatment response at a<jats:italic>group<\/jats:italic>level. Neither neurofilament light or heavy has shown a consistent treatment response to neuroprotective disease-modifying therapies, which will require further data from successful randomised controlled trials.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s00415-020-09917-x","type":"journal-article","created":{"date-parts":[[2020,5,23]],"date-time":"2020-05-23T08:02:53Z","timestamp":1590220973000},"page":"3212-3222","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Neurofilaments in progressive multiple sclerosis: a systematic review"],"prefix":"10.1007","volume":"268","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8197-0177","authenticated-orcid":false,"given":"Thomas","family":"Williams","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4671-6763","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7286-6901","authenticated-orcid":false,"given":"Jeremy","family":"Chataway","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,5,23]]},"reference":[{"key":"9917_CR1","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1212\/WNL.0000000000000560","volume":"83","author":"FD Lublin","year":"2014","unstructured":"Lublin FD, Reingold SC, Cohen JA et al (2014) Defining the clinical course of multiple sclerosis. 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In the last 3\u00a0years, JC has received support from the National Institute for Health Research (NIHR) EME Programme and Health Technology Assessment Programme (NIHR), the UK MS Society, the US National MS Society and the Rosetrees Trust. No funders had any role in this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"The manuscript does not contain primary clinical studies or patient data.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}]}}