{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:15:01Z","timestamp":1789496101016,"version":"build-2803163510"},"reference-count":36,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T00:00:00Z","timestamp":1692576000000},"content-version":"vor","delay-in-days":1328,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":["neurotherapeuticsjournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neurotherapeutics"],"published-print":{"date-parts":[[2020,1]]},"DOI":"10.1007\/s13311-019-00776-7","type":"journal-article","created":{"date-parts":[[2019,8,26]],"date-time":"2019-08-26T11:06:19Z","timestamp":1566817579000},"page":"200-207","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":50,"title":["Extending the Interval of Natalizumab Dosing: Is Efficacy Preserved?"],"prefix":"10.1016","volume":"17","author":[{"given":"Marinella","family":"Clerico","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania Federica","family":"De Mercanti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Signori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Iudicello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Cordioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Signoriello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Lus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Bonavita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Lavorgna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia Teresa","family":"Maniscalco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Curti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Lorefice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Cocco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviana","family":"Nociti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Mirabella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damiano","family":"Baroncini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Mataluni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doriana","family":"Landi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Petruzzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Lanzillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Gandoglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Laroni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Frangiamore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Sartori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Cavalla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianfranco","family":"Costantini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Pia","family":"Sormani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruggero","family":"Capra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1007\/s13311-019-00776-7_bib1","doi-asserted-by":"crossref","unstructured":"St\u00fcve O, Bennett JL. Pharmacological properties, toxicology and scientific rationale for the use of natalizumab (Tysabri\u00ae) in inflammatory diseases. CNS Drug Rev. 2007 Spring;13(1):79\u201395.","DOI":"10.1111\/j.1527-3458.2007.00003.x"},{"key":"10.1007\/s13311-019-00776-7_bib2","doi-asserted-by":"crossref","unstructured":"Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006;354(9):899\u2013910. Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/16510744. Accessed 27 May 2019","DOI":"10.1056\/NEJMoa044397"},{"key":"10.1007\/s13311-019-00776-7_bib3","doi-asserted-by":"crossref","unstructured":"Rudick RA, Stuart WH, Calabresi PA, Confavreux C, Galetta SL, Radue E-W, et al. Natalizumab plus Interferon Beta-1a for Relapsing Multiple Sclerosis. N Engl J Med. 2006;354(9):911\u201323.","DOI":"10.1056\/NEJMoa044396"},{"key":"10.1007\/s13311-019-00776-7_bib4","doi-asserted-by":"crossref","unstructured":"Sehr T, Proschmann U, Thomas K, Marggraf M, Straube E, Reichmann H, et al. New insights into the pharmacokinetics and pharmacodynamics of natalizumab treatment for patients with multiple sclerosis, obtained from clinical and in vitro studies. J Neuroinflammation. 2016;13(1):164. https:\/\/doi.org\/10.1186\/s12974-016-0635-2","DOI":"10.1186\/s12974-016-0635-2"},{"issue":"4","key":"10.1007\/s13311-019-00776-7_bib5","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1056\/NEJMoa051782","article-title":"Progressive Multifocal Leukoencephalopathy Complicating Treatment with Natalizumab and Interferon Beta-1a for Multiple Sclerosis","volume":"353","author":"Kleinschmidt-DeMasters","year":"2005","journal-title":"N Engl J Med"},{"key":"10.1007\/s13311-019-00776-7_bib6","doi-asserted-by":"crossref","unstructured":"Langer-Gould A, Atlas SW, Green AJ, Bollen AW, Pelletier D. Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med 2005;353(4):375\u201381.","DOI":"10.1056\/NEJMoa051847"},{"key":"10.1007\/s13311-019-00776-7_bib7","doi-asserted-by":"crossref","unstructured":"Tan CS, Koralnik IJ. Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis. Lancet Neurol. 2010;9:425\u201337.","DOI":"10.1016\/S1474-4422(10)70040-5"},{"key":"10.1007\/s13311-019-00776-7_bib8","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1586\/14737175.4.4.571","article-title":"Natalizumab: \u03b14-integrin antagonist selective adhesion molecule inhibitors for MS","author":"Rudick","year":"2004","journal-title":"Expert Review of Neurotherapeutics"},{"issue":"5","key":"10.1007\/s13311-019-00776-7_bib9","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1212\/01.wnl.0000341766.59028.9d","article-title":"Effect of plasma exchange in accelerating natalizumab clearance and restoring leukocyte function","volume":"72","author":"Khatri","year":"2009","journal-title":"Neurology."},{"key":"10.1007\/s13311-019-00776-7_bib10","doi-asserted-by":"crossref","unstructured":"Cofield SS, Salter A, Tyry T, Crowe C, Cutter GR, Fox RJ, et al. Perspectives on marijuana use and effectiveness: A survey of NARCOMS participants. Neurol Clin Pract. 2017;7(4):333\u2013343. https:\/\/doi.org\/10.1212\/CPJ.0000000000000383","DOI":"10.1212\/CPJ.0000000000000383"},{"key":"10.1007\/s13311-019-00776-7_bib11","doi-asserted-by":"crossref","unstructured":"Rispens T, Vennegoor A, Wolbink GJ, Polman CH, Killestein J. Natalizumab remains detectable in patients with multiple sclerosis long after treatment is stopped. Mult Scler. 2012;18(16):899\u2013901. https:\/\/doi.org\/10.1177\/1352458511431073","DOI":"10.1177\/1352458511431073"},{"key":"10.1007\/s13311-019-00776-7_bib12","doi-asserted-by":"crossref","unstructured":"Wipfler P, Harrer A, Pilz G, Oppermann K, Afazel S, Haschke-Becher E, et al. Natalizumab saturation: Biomarker for individual treatment holiday after natalizumab withdrawal? Acta Neurol Scand. 2014;129(3):e12\u20135. https:\/\/doi.org\/10.1111\/ane.12182","DOI":"10.1111\/ane.12182"},{"key":"10.1007\/s13311-019-00776-7_bib13","doi-asserted-by":"crossref","unstructured":"van Kempen ZLE, Leurs CE, Witte BI, de Vries A, Wattjes MP, Rispens T, et al. The majority of natalizumab-treated MS patients have high natalizumab concentrations at time of re-dosing. Mult Scler. 2018;24(6):805\u2013810. https:\/\/doi.org\/10.1177\/1352458517708464","DOI":"10.1177\/1352458517708464"},{"issue":"11","key":"10.1007\/s13311-019-00776-7_bib14","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1212\/WNL.0b013e31822e55e7","article-title":"Immune reconstitution inflammatory syndrome in natalizumab-associated PML","volume":"77","author":"Tan","year":"2011","journal-title":"Neurology."},{"key":"10.1007\/s13311-019-00776-7_bib15","unstructured":"Zhovtis Ryerson L, Frohman TC, Foley J, Kister I, Weinstock-Guttman B, Tornatore C, et al. Extended interval dosing of natalizumab in multiple sclerosis. J Neurol Neurosurg Psychiatry 2016;1\u20135. Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/26917698. Accessed 27 May 2019"},{"issue":"17","key":"10.1007\/s13311-019-00776-7_bib16","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1212\/WNL.0000000000000355","article-title":"MS disease activity in RESTORE: A randomized 24-week natalizumab treatment interruption study","volume":"82","author":"Fox","year":"2014","journal-title":"Neurology."},{"key":"10.1007\/s13311-019-00776-7_bib17","doi-asserted-by":"crossref","unstructured":"Harrer A, Pilz G, Einhaeupl M, Oppermann K, Hitzl W, Wipfler P, et al. Lymphocyte subsets show different response patterns to in vivo bound natalizumab-a flow cytometric study on patients with multiple sclerosis. PLoS One. 2012;7(2):e31784. https:\/\/doi.org\/10.1371\/journal.pone.0031784","DOI":"10.1371\/journal.pone.0031784"},{"key":"10.1007\/s13311-019-00776-7_bib18","unstructured":"European Medicines Agency. European Medicines Agency recommends additional measures to better manage risk of progressive multifocal leukoencephalopathy (PML) with Tysabri [Internet]. [cited 2018 Jun 16]. Available from: http:\/\/www.ema.europa.eu\/ema\/index.jsp?curl=pages\/news_and_events\/news\/2010\/01\/news_detail_000987.jsp&mid=WC0b01ac058004d5c1"},{"key":"10.1007\/s13311-019-00776-7_bib19","doi-asserted-by":"crossref","unstructured":"Kappos L, Bates D, Edan G, Eraksoy M, Garcia-Merino A, Grigoriadis N, et al. Natalizumab treatment for multiple sclerosis: Updated recommendations for patient selection and monitoring. Lancet Neurol 2011;10(8):745\u201358. https:\/\/doi.org\/10.1016\/S1474-4422(11)70149-1","DOI":"10.1016\/S1474-4422(11)70149-1"},{"key":"10.1007\/s13311-019-00776-7_bib20","doi-asserted-by":"crossref","unstructured":"Bloomgren G, Richman S, Hotermans C, Subramanyam M, Goelz S, Natarajan A, et al. Risk of Natalizumab-Associated Progressive Multifocal Leukoencephalopathy. N Engl J Med. 2012;366(20):1870\u201380. Available from: http:\/\/www.nejm.org\/doi\/abs\/10.1056\/NEJMoa1107829. Accessed 27 May 2019","DOI":"10.1056\/NEJMoa1107829"},{"key":"10.1007\/s13311-019-00776-7_bib21","doi-asserted-by":"crossref","unstructured":"Bomprezzi R, Pawate S. Extended interval dosing of natalizumab: A two-center, 7-year experience. Ther Adv Neurol Disord. 2014;7(5):227\u201331. https:\/\/doi.org\/10.1177\/1756285614540224","DOI":"10.1177\/1756285614540224"},{"key":"10.1007\/s13311-019-00776-7_bib22","doi-asserted-by":"crossref","unstructured":"Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 2018;17(2):162\u201373.","DOI":"10.1016\/S1474-4422(17)30470-2"},{"issue":"11","key":"10.1007\/s13311-019-00776-7_bib23","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1212\/WNL.33.11.1444","article-title":"Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS)","volume":"33","author":"Kurtzke","year":"1983","journal-title":"Neurology."},{"key":"10.1007\/s13311-019-00776-7_bib24","unstructured":"Lucchetta RC, Tonin FS, Borba HHL, Leonart LP, Ferreira VL, Bonetti AF, et al. Disease-Modifying Therapies for Relapsing-Remitting Multiple Sclerosis: A Network Meta-Analysis. CNS Drugs. 2018. Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30014314. Accessed 27 May 2019"},{"key":"10.1007\/s13311-019-00776-7_bib25","doi-asserted-by":"crossref","unstructured":"S\u00f8rensen PS, Bertolotto A, Edan G, Giovannoni G, Gold R, Havrdova E, et al. Risk stratification for progressive multifocal leukoencephalopathy in patients treated with natalizumab. Mult Scler 2012;18(2):143\u201352. Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22312009. Accessed 27 May 2019","DOI":"10.1177\/1352458511435105"},{"key":"10.1007\/s13311-019-00776-7_bib26","unstructured":"https:\/\/chefarztfrau.de\/?page_id=716 [Internet]. [cited 2018 May 31]. Available from: https:\/\/chefarztfrau.de\/?page_id=716"},{"key":"10.1007\/s13311-019-00776-7_bib27","unstructured":"EMA confirms recommendations to minimise risk of brain infection PML with Tysabri - EMA\/137488\/2016."},{"issue":"22","key":"10.1007\/s13311-019-00776-7_bib28","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1212\/WNL.0b013e31821e7c8a","article-title":"Disease activity return during natalizumab treatment interruption in patients with multiple sclerosis","volume":"76","author":"O'Connor","year":"2011","journal-title":"Neurology."},{"issue":"3","key":"10.1007\/s13311-019-00776-7_bib29","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1002\/ana.22083","article-title":"Considerations on discontinuing natalizumab for the treatment of multiple sclerosis","volume":"68","author":"Berger","year":"2010","journal-title":"Ann Neurol"},{"issue":"6","key":"10.1007\/s13311-019-00776-7_bib30","doi-asserted-by":"crossref","first-page":"e297","DOI":"10.1212\/NXI.0000000000000297","article-title":"Risk of relapse after natalizumab withdrawal: Results from the French TYSEDMUS cohort","volume":"3","author":"Papeix","year":"2016","journal-title":"Neurol Neuroimmunol Neuroinflammation"},{"issue":"4","key":"10.1007\/s13311-019-00776-7_bib31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/brb3.671","article-title":"Catastrophic outcome of patients with a rebound after Natalizumab treatment discontinuation","volume":"7","author":"Gonz\u00e1lez-Suarez","year":"2017","journal-title":"Brain Behav"},{"issue":"8","key":"10.1007\/s13311-019-00776-7_bib32","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1001\/jamaneurol.2014.1200","article-title":"Treatment of Relapsing-Remitting Multiple Sclerosis After 24 Doses of Natalizumab: Evidence From an Italian Spontaneous, Prospective, and Observational Study (the TY-STOP Study)","volume":"71","author":"Clerico","year":"2014","journal-title":"JAMA Neurol"},{"key":"10.1007\/s13311-019-00776-7_bib33","doi-asserted-by":"crossref","unstructured":"Van Kempen ZLE, Leurs CE, Vennegoor A, Wattjes MP, Rispens T, Uitdehaag BMJ, et al. Natalizumab-associated progressive multifocal leukoencephalopathy is not preceded by elevated drug concentrations. Mult Scler J. 2017;23(7):995\u2013999. https:\/\/doi.org\/10.1177\/1352458516684023","DOI":"10.1177\/1352458516684023"},{"key":"10.1007\/s13311-019-00776-7_bib34","doi-asserted-by":"crossref","unstructured":"Zhovtis, Ryerson L, Foley J CIKICGMRGJLXREYBRZHCHP-RCN. Natalizumab Extended Interval Dosing (EID) Is Associated with a Significant Reduction in Progressive Multifocal Leukoencephalopathy (PML) Risk Compared with Standard Interval Dosing (SID): Analyses of TOUCH\u00ae Prescribing Program Data. In: American Academy of Neurology. 2018.","DOI":"10.1016\/j.neurol.2019.01.272"},{"issue":"6","key":"10.1007\/s13311-019-00776-7_bib35","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1007\/s00415-014-7325-8","article-title":"Recurrence or rebound of clinical relapses after discontinuation of natalizumab therapy in highly active MS patients","volume":"261","author":"Sorensen","year":"2014","journal-title":"J Neurol"},{"key":"10.1007\/s13311-019-00776-7_bib36","unstructured":"A Study to Evaluate Efficacy, Safety, and Tolerability of 6-Week Extended Interval Dosing of Natalizumab (BG00002) in Participants With Relapsing-Remitting Multiple Sclerosis (RRMS) Switching From Treatment With 4-Week Natalizumab Standard Interval Dosing [Internet]. [cited 2019 Jul 30]. Available from: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03689972?term=NCT03689972&rank=1"}],"container-title":["Neurotherapeutics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s13311-019-00776-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s13311-019-00776-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1878747923013909?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1878747923013909?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s13311-019-00776-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T06:59:26Z","timestamp":1761807566000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1878747923013909"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["S1878747923013909"],"URL":"https:\/\/doi.org\/10.1007\/s13311-019-00776-7","relation":{},"ISSN":["1878-7479"],"issn-type":[{"value":"1878-7479","type":"print"}],"subject":[],"published":{"date-parts":[[2020,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Extending the Interval of Natalizumab Dosing: Is Efficacy Preserved?","name":"articletitle","label":"Article Title"},{"value":"Neurotherapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1007\/s13311-019-00776-7","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2020 The American Society for Experimental NeuroTherapeutics, Inc. Published by Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}