Neurofilament light levels are associated with long-term outcomes in multiple sclerosis
Background: Neurofilament light chain (NfL) is a promising marker of disease activity/treatment response in multiple sclerosis (MS), although its predictive value for long-term clinical outcomes remains unclear. Objective: We measured NfL from a phase 3 trial in relapsing-remitting MS and investigat...
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| Veröffentlicht in: | Multiple sclerosis 2020-11, Vol.26 (13), p.1691-1699 |
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| creator | Kuhle, Jens Plavina, Tatiana Barro, Christian Disanto, Giulio Sangurdekar, Dipen Singh, Carol M de Moor, Carl Engle, Bob Kieseier, Bernd C Fisher, Elizabeth Kappos, Ludwig Rudick, Richard A Goyal, Jaya |
| description | Background:
Neurofilament light chain (NfL) is a promising marker of disease activity/treatment response in multiple sclerosis (MS), although its predictive value for long-term clinical outcomes remains unclear.
Objective:
We measured NfL from a phase 3 trial in relapsing-remitting MS and investigated its association with outcomes after 8 and 15 years.
Methods:
NfL concentrations were measured by single molecule array assay in cerebrospinal fluid (CSF) from MS patients (n = 235) in a 2-year randomized clinical trial (RCT) of intramuscular interferon β-1a, and in serum (n = 164) from the extension study.
Results:
Year 2 CSF and Year 3 serum NfL were associated with brain parenchymal fraction (BPF) change over 8 years (p |
| doi_str_mv | 10.1177/1352458519885613 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7604552</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_1352458519885613</sage_id><sourcerecordid>2454367384</sourcerecordid><originalsourceid>FETCH-LOGICAL-c462t-74f40841d9e5410efff51cc81eac653c9dca8d9e7b4bd9b3a660f7df1d4a42e03</originalsourceid><addsrcrecordid>eNp1kc1LHTEUxUOpVGu7d1UC3XQzmjv5mtkIIv0QxG5augx5mZv3IpnJazKj-N838qy1gpskcH73JCeHkCNgxwBanwCXrZCdhL7rpAL-ihyA0LphvWav67nKzb2-T96Wcs0Y05rLN2Sfg-qYauGA_LrCJScfoh1xmmkM601d8QZjoTYjtaUkF-yMA70N84bGNK2bGfNI0zK7NGKhYaLjEuewjUiLi5hTCeUd2fM2Fnz_sB-Sn18-_zj_1lx-_3pxfnbZOKHaudHCC9YJGHqUAhh67yU41wFapyR3_eBsV0W9EquhX3GrFPN68DAIK1pk_JCc7ny3y2rEwdUQ2UazzWG0-c4kG8z_yhQ2Zp1ujFZMSNlWg08PBjn9XrDMZgzFYYx2wrQU03KAvpWc64p-fIZepyVPNZ6pLQiuNO9EpdiOcvUjSkb_-Bhg5r4187y1OvLhaYjHgb81VaDZAcWu8d-tLxr-Aa3ZoX8</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2454367384</pqid></control><display><type>article</type><title>Neurofilament light levels are associated with long-term outcomes in multiple sclerosis</title><source>SAGE Complete A-Z List</source><creator>Kuhle, Jens ; Plavina, Tatiana ; Barro, Christian ; Disanto, Giulio ; Sangurdekar, Dipen ; Singh, Carol M ; de Moor, Carl ; Engle, Bob ; Kieseier, Bernd C ; Fisher, Elizabeth ; Kappos, Ludwig ; Rudick, Richard A ; Goyal, Jaya</creator><creatorcontrib>Kuhle, Jens ; Plavina, Tatiana ; Barro, Christian ; Disanto, Giulio ; Sangurdekar, Dipen ; Singh, Carol M ; de Moor, Carl ; Engle, Bob ; Kieseier, Bernd C ; Fisher, Elizabeth ; Kappos, Ludwig ; Rudick, Richard A ; Goyal, Jaya</creatorcontrib><description>Background:
Neurofilament light chain (NfL) is a promising marker of disease activity/treatment response in multiple sclerosis (MS), although its predictive value for long-term clinical outcomes remains unclear.
Objective:
We measured NfL from a phase 3 trial in relapsing-remitting MS and investigated its association with outcomes after 8 and 15 years.
Methods:
NfL concentrations were measured by single molecule array assay in cerebrospinal fluid (CSF) from MS patients (n = 235) in a 2-year randomized clinical trial (RCT) of intramuscular interferon β-1a, and in serum (n = 164) from the extension study.
Results:
Year 2 CSF and Year 3 serum NfL were associated with brain parenchymal fraction (BPF) change over 8 years (p < 0.0001, r = −0.46; p < 0.05. r = −0.36, respectively) and were predictive of reaching Expanded Disability Status Scale (EDSS) ⩾ 6.0 at Year 8 (odds ratio (OR) (upper vs lower tertile) = 3.4; 95% confidence interval (CI) = 1.2–9.9, p < 0.05; OR = 11.0, 95% CI = 2.0–114.6; p < 0.01, respectively). Serum NfL concentration (Year 4) was predictive of reaching EDSS score ⩾6.0 at 15 years (OR (upper vs lower tertile) = 4.9; 95% CI = 1.4–20.4; p < 0.05). NfL concentrations were complementary to 2-year BPF change in predicting long-term outcomes.
Conclusion:
Serum and CSF NfL concentrations were associated with long-term clinical outcomes in MS patients and are promising biomarkers for disease severity stratification supporting treatment decisions.</description><identifier>ISSN: 1352-4585</identifier><identifier>EISSN: 1477-0970</identifier><identifier>DOI: 10.1177/1352458519885613</identifier><identifier>PMID: 31680621</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Cerebrospinal fluid ; Clinical outcomes ; Interferon ; Multiple sclerosis ; Original Research Papers ; Patients</subject><ispartof>Multiple sclerosis, 2020-11, Vol.26 (13), p.1691-1699</ispartof><rights>The Author(s), 2019</rights><rights>The Author(s), 2019 2019 SAGE Publications</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c462t-74f40841d9e5410efff51cc81eac653c9dca8d9e7b4bd9b3a660f7df1d4a42e03</citedby><cites>FETCH-LOGICAL-c462t-74f40841d9e5410efff51cc81eac653c9dca8d9e7b4bd9b3a660f7df1d4a42e03</cites><orcidid>0000-0003-4175-5509</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/1352458519885613$$EPDF$$P50$$Gsage$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/1352458519885613$$EHTML$$P50$$Gsage$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,21817,27922,27923,43619,43620</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31680621$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kuhle, Jens</creatorcontrib><creatorcontrib>Plavina, Tatiana</creatorcontrib><creatorcontrib>Barro, Christian</creatorcontrib><creatorcontrib>Disanto, Giulio</creatorcontrib><creatorcontrib>Sangurdekar, Dipen</creatorcontrib><creatorcontrib>Singh, Carol M</creatorcontrib><creatorcontrib>de Moor, Carl</creatorcontrib><creatorcontrib>Engle, Bob</creatorcontrib><creatorcontrib>Kieseier, Bernd C</creatorcontrib><creatorcontrib>Fisher, Elizabeth</creatorcontrib><creatorcontrib>Kappos, Ludwig</creatorcontrib><creatorcontrib>Rudick, Richard A</creatorcontrib><creatorcontrib>Goyal, Jaya</creatorcontrib><title>Neurofilament light levels are associated with long-term outcomes in multiple sclerosis</title><title>Multiple sclerosis</title><addtitle>Mult Scler</addtitle><description>Background:
Neurofilament light chain (NfL) is a promising marker of disease activity/treatment response in multiple sclerosis (MS), although its predictive value for long-term clinical outcomes remains unclear.
Objective:
We measured NfL from a phase 3 trial in relapsing-remitting MS and investigated its association with outcomes after 8 and 15 years.
Methods:
NfL concentrations were measured by single molecule array assay in cerebrospinal fluid (CSF) from MS patients (n = 235) in a 2-year randomized clinical trial (RCT) of intramuscular interferon β-1a, and in serum (n = 164) from the extension study.
Results:
Year 2 CSF and Year 3 serum NfL were associated with brain parenchymal fraction (BPF) change over 8 years (p < 0.0001, r = −0.46; p < 0.05. r = −0.36, respectively) and were predictive of reaching Expanded Disability Status Scale (EDSS) ⩾ 6.0 at Year 8 (odds ratio (OR) (upper vs lower tertile) = 3.4; 95% confidence interval (CI) = 1.2–9.9, p < 0.05; OR = 11.0, 95% CI = 2.0–114.6; p < 0.01, respectively). Serum NfL concentration (Year 4) was predictive of reaching EDSS score ⩾6.0 at 15 years (OR (upper vs lower tertile) = 4.9; 95% CI = 1.4–20.4; p < 0.05). NfL concentrations were complementary to 2-year BPF change in predicting long-term outcomes.
Conclusion:
Serum and CSF NfL concentrations were associated with long-term clinical outcomes in MS patients and are promising biomarkers for disease severity stratification supporting treatment decisions.</description><subject>Cerebrospinal fluid</subject><subject>Clinical outcomes</subject><subject>Interferon</subject><subject>Multiple sclerosis</subject><subject>Original Research Papers</subject><subject>Patients</subject><issn>1352-4585</issn><issn>1477-0970</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AFRWT</sourceid><recordid>eNp1kc1LHTEUxUOpVGu7d1UC3XQzmjv5mtkIIv0QxG5augx5mZv3IpnJazKj-N838qy1gpskcH73JCeHkCNgxwBanwCXrZCdhL7rpAL-ihyA0LphvWav67nKzb2-T96Wcs0Y05rLN2Sfg-qYauGA_LrCJScfoh1xmmkM601d8QZjoTYjtaUkF-yMA70N84bGNK2bGfNI0zK7NGKhYaLjEuewjUiLi5hTCeUd2fM2Fnz_sB-Sn18-_zj_1lx-_3pxfnbZOKHaudHCC9YJGHqUAhh67yU41wFapyR3_eBsV0W9EquhX3GrFPN68DAIK1pk_JCc7ny3y2rEwdUQ2UazzWG0-c4kG8z_yhQ2Zp1ujFZMSNlWg08PBjn9XrDMZgzFYYx2wrQU03KAvpWc64p-fIZepyVPNZ6pLQiuNO9EpdiOcvUjSkb_-Bhg5r4187y1OvLhaYjHgb81VaDZAcWu8d-tLxr-Aa3ZoX8</recordid><startdate>20201101</startdate><enddate>20201101</enddate><creator>Kuhle, Jens</creator><creator>Plavina, Tatiana</creator><creator>Barro, Christian</creator><creator>Disanto, Giulio</creator><creator>Sangurdekar, Dipen</creator><creator>Singh, Carol M</creator><creator>de Moor, Carl</creator><creator>Engle, Bob</creator><creator>Kieseier, Bernd C</creator><creator>Fisher, Elizabeth</creator><creator>Kappos, Ludwig</creator><creator>Rudick, Richard A</creator><creator>Goyal, Jaya</creator><general>SAGE Publications</general><general>Sage Publications Ltd</general><scope>AFRWT</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4175-5509</orcidid></search><sort><creationdate>20201101</creationdate><title>Neurofilament light levels are associated with long-term outcomes in multiple sclerosis</title><author>Kuhle, Jens ; Plavina, Tatiana ; Barro, Christian ; Disanto, Giulio ; Sangurdekar, Dipen ; Singh, Carol M ; de Moor, Carl ; Engle, Bob ; Kieseier, Bernd C ; Fisher, Elizabeth ; Kappos, Ludwig ; Rudick, Richard A ; Goyal, Jaya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c462t-74f40841d9e5410efff51cc81eac653c9dca8d9e7b4bd9b3a660f7df1d4a42e03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Cerebrospinal fluid</topic><topic>Clinical outcomes</topic><topic>Interferon</topic><topic>Multiple sclerosis</topic><topic>Original Research Papers</topic><topic>Patients</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kuhle, Jens</creatorcontrib><creatorcontrib>Plavina, Tatiana</creatorcontrib><creatorcontrib>Barro, Christian</creatorcontrib><creatorcontrib>Disanto, Giulio</creatorcontrib><creatorcontrib>Sangurdekar, Dipen</creatorcontrib><creatorcontrib>Singh, Carol M</creatorcontrib><creatorcontrib>de Moor, Carl</creatorcontrib><creatorcontrib>Engle, Bob</creatorcontrib><creatorcontrib>Kieseier, Bernd C</creatorcontrib><creatorcontrib>Fisher, Elizabeth</creatorcontrib><creatorcontrib>Kappos, Ludwig</creatorcontrib><creatorcontrib>Rudick, Richard A</creatorcontrib><creatorcontrib>Goyal, Jaya</creatorcontrib><collection>Sage Journals GOLD Open Access 2024</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Multiple sclerosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kuhle, Jens</au><au>Plavina, Tatiana</au><au>Barro, Christian</au><au>Disanto, Giulio</au><au>Sangurdekar, Dipen</au><au>Singh, Carol M</au><au>de Moor, Carl</au><au>Engle, Bob</au><au>Kieseier, Bernd C</au><au>Fisher, Elizabeth</au><au>Kappos, Ludwig</au><au>Rudick, Richard A</au><au>Goyal, Jaya</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neurofilament light levels are associated with long-term outcomes in multiple sclerosis</atitle><jtitle>Multiple sclerosis</jtitle><addtitle>Mult Scler</addtitle><date>2020-11-01</date><risdate>2020</risdate><volume>26</volume><issue>13</issue><spage>1691</spage><epage>1699</epage><pages>1691-1699</pages><issn>1352-4585</issn><eissn>1477-0970</eissn><abstract>Background:
Neurofilament light chain (NfL) is a promising marker of disease activity/treatment response in multiple sclerosis (MS), although its predictive value for long-term clinical outcomes remains unclear.
Objective:
We measured NfL from a phase 3 trial in relapsing-remitting MS and investigated its association with outcomes after 8 and 15 years.
Methods:
NfL concentrations were measured by single molecule array assay in cerebrospinal fluid (CSF) from MS patients (n = 235) in a 2-year randomized clinical trial (RCT) of intramuscular interferon β-1a, and in serum (n = 164) from the extension study.
Results:
Year 2 CSF and Year 3 serum NfL were associated with brain parenchymal fraction (BPF) change over 8 years (p < 0.0001, r = −0.46; p < 0.05. r = −0.36, respectively) and were predictive of reaching Expanded Disability Status Scale (EDSS) ⩾ 6.0 at Year 8 (odds ratio (OR) (upper vs lower tertile) = 3.4; 95% confidence interval (CI) = 1.2–9.9, p < 0.05; OR = 11.0, 95% CI = 2.0–114.6; p < 0.01, respectively). Serum NfL concentration (Year 4) was predictive of reaching EDSS score ⩾6.0 at 15 years (OR (upper vs lower tertile) = 4.9; 95% CI = 1.4–20.4; p < 0.05). NfL concentrations were complementary to 2-year BPF change in predicting long-term outcomes.
Conclusion:
Serum and CSF NfL concentrations were associated with long-term clinical outcomes in MS patients and are promising biomarkers for disease severity stratification supporting treatment decisions.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>31680621</pmid><doi>10.1177/1352458519885613</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-4175-5509</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Cerebrospinal fluid Clinical outcomes Interferon Multiple sclerosis Original Research Papers Patients |
| title | Neurofilament light levels are associated with long-term outcomes in multiple sclerosis |
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