{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T23:22:31Z","timestamp":1777936951313,"version":"3.51.4"},"reference-count":15,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2016,12,13]],"date-time":"2016-12-13T00:00:00Z","timestamp":1481587200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100008358","name":"De Hersenstichting","doi-asserted-by":"crossref","award":["HA2015.01.05"],"award-info":[{"award-number":["HA2015.01.05"]}],"id":[{"id":"10.13039\/501100008358","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>In recent years, a small but increasing number of neurologists choose to extend dose intervals of natalizumab with the aim of reducing the risk of progressive multifocal leukoencephalopathy (PML). This idea is based on the hypothesis that high drug concentrations increase the risk of PML.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>We investigated the relation between longitudinal natalizumab concentrations in patients who developed PML and patients who did not develop PML.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>In a prospective observational cohort study of 219 patients with relapsing\u2013remitting multiple sclerosis treated with natalizumab, serum samples were taken every 12\u2009weeks prior to natalizumab infusion. In this cohort, 5 patients developed PML and were matched with 10 patients from the cohort who did not develop PML. Natalizumab concentrations were measured in available samples, and the longitudinal results were compared between the two patient groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Mean natalizumab concentrations in the five patients developing PML was 18.9\u2009\u00b5g\/mL (standard deviation (SD): \u00b113.4) versus 23.8\u2009\u00b5g\/mL (SD: \u00b111.5) of the control patients. Furthermore, we did not observe a clear rise in concentration levels in patients subsequently developing PML.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Our results provide preliminary evidence that contradicts the hypothesis that exposure to elevated concentrations of natalizumab is a relevant risk factor of developing PML.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1352458516684023","type":"journal-article","created":{"date-parts":[[2017,1,19]],"date-time":"2017-01-19T06:19:06Z","timestamp":1484806746000},"page":"995-999","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":11,"title":["Natalizumab-associated progressive multifocal leukoencephalopathy is not preceded by elevated drug concentrations"],"prefix":"10.1177","volume":"23","author":[{"given":"Zo\u00e9 LE","family":"van Kempen","sequence":"first","affiliation":[{"name":"Department of Neurology, Neuroscience Campus Amsterdam, VUmc MS Center Amsterdam, VU University Medical Center Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cyra E","family":"Leurs","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neuroscience Campus Amsterdam, VUmc MS Center Amsterdam, VU University Medical Center Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anke","family":"Vennegoor","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neuroscience Campus Amsterdam, VUmc MS Center Amsterdam, VU University Medical Center Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mike P","family":"Wattjes","sequence":"additional","affiliation":[{"name":"Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VUmc MS Center Amsterdam, VU University Medical Center Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theo","family":"Rispens","sequence":"additional","affiliation":[{"name":"Landsteiner Laboratory, Department of Immunology, Sanquin Research, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard MJ","family":"Uitdehaag","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neuroscience Campus Amsterdam, VUmc MS Center Amsterdam, VU University Medical Center Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joep","family":"Killestein","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neuroscience Campus Amsterdam, VUmc MS Center Amsterdam, VU University Medical Center Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2016,12,13]]},"reference":[{"key":"bibr1-1352458516684023","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa044397"},{"key":"bibr2-1352458516684023","unstructured":"EMA. Updated recommendations to minimise the risk of the rare brain infection PML with Tysabri, 2016, http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Press_release\/2016\/02\/WC500201891.pdf (accessed 12 February 2016)."},{"key":"bibr3-1352458516684023","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1107829"},{"issue":"2","key":"bibr4-1352458516684023","first-page":"117","volume":"87","author":"McGuigan C","year":"2016","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"bibr5-1352458516684023","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.157"},{"key":"bibr6-1352458516684023","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.7.1.123"},{"key":"bibr7-1352458516684023","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000341766.59028.9d"},{"key":"bibr8-1352458516684023","doi-asserted-by":"publisher","DOI":"10.1177\/1352458512460604"},{"key":"bibr9-1352458516684023","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2015-312940"},{"key":"bibr10-1352458516684023","doi-asserted-by":"publisher","DOI":"10.1177\/1756285614540224"},{"key":"bibr11-1352458516684023","doi-asserted-by":"publisher","DOI":"10.1177\/1352458514541507"},{"key":"bibr12-1352458516684023","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2011.01.001"},{"key":"bibr13-1352458516684023","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2013.02.002"},{"issue":"14","key":"bibr14-1352458516684023","volume":"84","author":"Foley J","year":"2015","journal-title":"Neurology"},{"key":"bibr15-1352458516684023","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22074"}],"container-title":["Multiple Sclerosis Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1352458516684023","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1352458516684023","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1352458516684023","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T03:49:04Z","timestamp":1777693744000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1352458516684023"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,13]]},"references-count":15,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2017,6]]}},"alternative-id":["10.1177\/1352458516684023"],"URL":"https:\/\/doi.org\/10.1177\/1352458516684023","relation":{},"ISSN":["1352-4585","1477-0970"],"issn-type":[{"value":"1352-4585","type":"print"},{"value":"1477-0970","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,13]]}}}