{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:50:25Z","timestamp":1792698625592,"version":"4.5.0"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,10,24]],"date-time":"2014-10-24T00:00:00Z","timestamp":1414108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The increased risk of progressive multifocal leukoencephalopathy (PML) with natalizumab treatment is associated with the presence of anti\u2013JC virus (JCV) antibodies. We analyzed whether anti\u2010JCV antibody levels, measured as index, may further define PML risk in seropositive patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The association between serum or plasma anti\u2010JCV antibody levels and PML risk was examined in anti\u2010JCV antibody\u2013positive multiple sclerosis (MS) patients from natalizumab clinical studies and postmarketing sources. For PML and non\u2010PML patients, the probabilities of having an index below and above a range of anti\u2010JCV antibody index thresholds were calculated using all available data and applied to the PML risk stratification algorithm. Longitudinal stability of anti\u2010JCV antibody index was also evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Anti\u2010JCV antibody index data were available for serum\/plasma samples collected &gt;6 months prior to PML diagnosis from 71 natalizumab\u2010treated PML patients and 2,522 non\u2010PML anti\u2010JCV antibody\u2013positive patients. In patients with no prior immunosuppressant use, anti\u2010JCV antibody index distribution was significantly higher in PML patients than in non\u2010PML patients (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Among patients who were anti\u2010JCV antibody negative at baseline in the AFFIRM and STRATIFY\u20101 trials, 97% remained consistently negative or below an index threshold of 1.5 over 18 months. Retrospective analyses of pre\u2010PML samples collected longitudinally from PML patients displayed sustained higher anti\u2010JCV antibody index over time.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Anti\u2010JCV antibody levels in serum\/plasma, measured as index, may differentiate PML risk in anti\u2010JCV antibody\u2013positive MS patients with no prior immunosuppressant use. Continued evaluation of anti\u2010JCV antibody index and PML risk is warranted. Ann Neurol 2014;76:802\u2013812<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.24286","type":"journal-article","created":{"date-parts":[[2014,10,1]],"date-time":"2014-10-01T12:33:36Z","timestamp":1412166816000},"page":"802-812","source":"Crossref","is-referenced-by-count":408,"title":["Anti\u2013JC virus antibody levels in serum or plasma further define risk of natalizumab\u2010associated progressive multifocal leukoencephalopathy"],"prefix":"10.1002","volume":"76","author":[{"given":"Tatiana","family":"Plavina","sequence":"first","affiliation":[{"name":"Biogen Idec Cambridge MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meena","family":"Subramanyam","sequence":"additional","affiliation":[{"name":"Biogen Idec Cambridge MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Bloomgren","sequence":"additional","affiliation":[{"name":"Biogen Idec Cambridge MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Richman","sequence":"additional","affiliation":[{"name":"Biogen Idec Cambridge MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Pace","sequence":"additional","affiliation":[{"name":"Biogen Idec Cambridge MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Lee","sequence":"additional","affiliation":[{"name":"Biogen Idec Cambridge MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Schlain","sequence":"additional","affiliation":[{"name":"Biogen Idec Cambridge MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Campagnolo","sequence":"additional","affiliation":[{"name":"Biogen Idec Cambridge MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shibeshih","family":"Belachew","sequence":"additional","affiliation":[{"name":"Biogen Idec Cambridge MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry","family":"Ticho","sequence":"additional","affiliation":[{"name":"Biogen Idec Cambridge MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,10,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa044397"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000541"},{"key":"e_1_2_8_4_1","article-title":"Efficacy and safety of natalizumab in multiple sclerosis: interim observational programme results","author":"Butzkueven H","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1107829"},{"key":"e_1_2_8_6_1","unstructured":"Biogen Idec. 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JCV antibody index stratifies PML risk in natalizumab\u2010treated MS patients. Available at:https:\/\/cmscactrims.confex.com\/cmscactrims\/2013\/webprogram\/Paper1642.html. Accessed November 25 2013."},{"key":"e_1_2_8_18_1","unstructured":"PlavinaT SubramanyamM BloomgrenG et al. Use of anti\u2010JC virus antibody index to further define risk of PML in anti\u2010JCV antibody\u2010positive natalizumab\u2010treated patients with MS (0228). Presented at: 23rd Annual Meeting of the European Neurological Society; June 8\u201311 2013; Barcelona Spain."},{"key":"e_1_2_8_19_1","unstructured":"Focus Diagnostics. STRATIFY JCV DxSelect\u2122 prescribing information 2013. Available at:http:\/\/www.focusdx.com\/pdfs\/pi\/US\/EL1950.pdf. 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Use of the JC virus stratify assay in a cohort of natalizumab\u2010treated patients from Belgium. Comparative results between 2011 and 2012. 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