{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:02:11Z","timestamp":1792029731265,"version":"4.4.0"},"reference-count":16,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T00:00:00Z","timestamp":1585612800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/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":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"accepted":{"date-parts":[[2020,3,14]]},"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The Tysabri Observational Programme (TOP), which began &gt;10 years ago, is an open-label, multinational, prospective observational study evaluating the long-term safety and effectiveness of natalizumab in relapsing-remitting multiple sclerosis patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>These data provide a 10-year interim analysis of safety and effectiveness in TOP. Annualised relapse rates (ARRs) and disability progression\/improvement were analysed using the Poisson model and the Kaplan-Meier method, respectively. Analyses included patients on natalizumab and those who discontinued natalizumab but remained in TOP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>As of November 2017, TOP included 6148 patients. Overall, 829 patients (13.5%) experienced \u22651 serious adverse event (SAE), with infection the most common (4.1%). Fifty-three patients (0.9%) had confirmed progressive multifocal leukoencephalopathy. SAE data were consistent with natalizumab\u2019s known safety profile; no new safety signals were identified. A total of 3210 patients (52.2%) discontinued natalizumab; 2117 (34.4%) withdrew from TOP. Median time on natalizumab was 3.3 (range 0\u201311.6) years; median follow-up time was 5.2 (range 0\u201310.8) years. The on-natalizumab ARR was 0.15, a 92.5% reduction from the year before initiation. Ten-year cumulative probabilities of disability worsening and improvement were 27.8% and 33.1%, respectively. On-natalizumab ARRs were similar between patients who discontinued or remained on natalizumab, suggesting limited attrition bias.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Since the TOP 5-year interim analysis (December 2012), cohort size (6148 vs 4821), median exposure (3.3 vs 1.8 years) and median follow-up time (62 vs 26 months) have increased. This 10-year interim analysis further supports the robust real-world effectiveness and well-established safety profile of natalizumab.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT00493298\">NCT00493298<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jnnp-2019-322326","type":"journal-article","created":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T17:20:30Z","timestamp":1585675230000},"page":"660-668","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":160,"title":["Long-term safety and effectiveness of natalizumab treatment in clinical practice: 10 years of real-world data from the Tysabri Observational Program (TOP)"],"prefix":"10.1136","volume":"91","clinical-trial-number":[{"clinical-trial-number":"nct00493298","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Helmut","family":"Butzkueven","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludwig","family":"Kappos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"Wiendl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Trojano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Spelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ih","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachna","family":"Kasliwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seema","family":"Jaitly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nolan","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Ran","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Licata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2020,3,31]]},"reference":[{"key":"2024111108100772000_91.6.660.1","unstructured":"Tysabri (natalizumab) [summary of product characteristics] 2018."},{"key":"2024111108100772000_91.6.660.2","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1056\/NEJMoa044397","article-title":"A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis","volume":"354","author":"Polman","year":"2006","journal-title":"N Engl J Med"},{"key":"2024111108100772000_91.6.660.3","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.clineuro.2016.07.001","article-title":"Effectiveness and safety of natalizumab in real-world clinical practice: review of observational studies","volume":"149","author":"van Pesch","year":"2016","journal-title":"Clin Neurol Neurosurg"},{"key":"2024111108100772000_91.6.660.4","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1136\/jnnp-2013-306936","article-title":"Efficacy and safety of natalizumab in multiple sclerosis: interim observational programme results","volume":"85","author":"Butzkueven","year":"2014","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2024111108100772000_91.6.660.5","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.msard.2018.04.020","article-title":"Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting","volume":"24","author":"Trojano","year":"2018","journal-title":"Mult Scler Relat Disord"},{"key":"2024111108100772000_91.6.660.6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0144834"},{"key":"2024111108100772000_91.6.660.7","doi-asserted-by":"publisher","DOI":"10.1177\/1352458511399611"},{"key":"2024111108100772000_91.6.660.8","doi-asserted-by":"crossref","first-page":"3771","DOI":"10.1002\/cncr.29059","article-title":"Overview of breast cancer collaborative stage data items\u2014their definitions, quality, usage, and clinical implications: a review of SEER data for 2004-2010","volume":"120","author":"Howlader","year":"2014","journal-title":"Cancer"},{"key":"2024111108100772000_91.6.660.9","unstructured":"Ferlay J , Soerjomataram I , Ervik M .GLOBOCAN 2012 Cancer Incidence and Mortality Worldwide: IARC Cancerbase No. 11. Lyon, France International Agency for Research on Cancer; 2013."},{"key":"2024111108100772000_91.6.660.10","unstructured":". Tysabri (natalizumab) [prescribing information]. Cambridge, MA. Biogen; 2018."},{"key":"2024111108100772000_91.6.660.11","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1016\/j.ejca.2012.12.027","article-title":"Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012","volume":"49","author":"Ferlay","year":"2013","journal-title":"Eur J Cancer"},{"key":"2024111108100772000_91.6.660.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2013.02.002"},{"key":"2024111108100772000_91.6.660.13","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1056\/NEJMoa1107829","article-title":"Risk of natalizumab-associated progressive multifocal leukoencephalopathy","volume":"366","author":"Bloomgren","year":"2012","journal-title":"N Engl J Med"},{"key":"2024111108100772000_91.6.660.14","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/S1474-4422(17)30282-X","article-title":"Risk of natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: a retrospective analysis of data from four clinical studies","volume":"16","author":"Ho","year":"2017","journal-title":"Lancet Neurol"},{"key":"2024111108100772000_91.6.660.15","unstructured":"Physician information and management guidelines for multiple sclerosis patients on TYSABRI therapy. Version 17, 2017. Available: http:\/\/medicinesauthority.gov.mt\/file.aspx?f=3565 [Accessed 1 Mar 2019]."},{"key":"2024111108100772000_91.6.660.16","doi-asserted-by":"crossref","first-page":"628","DOI":"10.14336\/AD.2017.0103","article-title":"The biology of aging and cancer: a brief overview of shared and divergent molecular hallmarks","volume":"8","author":"Aunan","year":"2017","journal-title":"Aging Dis"}],"container-title":["Journal of Neurology, Neurosurgery &amp; Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jnnp-2019-322326","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T11:12:48Z","timestamp":1731323568000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnnp.bmj.com\/lookup\/doi\/10.1136\/jnnp-2019-322326"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,31]]},"references-count":16,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,5,15]]},"published-print":{"date-parts":[[2020,6]]}},"alternative-id":["10.1136\/jnnp-2019-322326"],"URL":"https:\/\/doi.org\/10.1136\/jnnp-2019-322326","relation":{},"ISSN":["0022-3050","1468-330X"],"issn-type":[{"value":"0022-3050","type":"print"},{"value":"1468-330X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,31]]}}}