{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T08:29:18Z","timestamp":1786350558342,"version":"build-2736575974"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Biogen Italia"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>EASIER 2 is a multicenter, observational, cross-sectional study conducted in 14 Italian multiple sclerosis (MS) centers to evaluate patient and healthcare professional (HCP) time, healthcare resource consumption, costs, and patient quality of life (QoL) associated with subcutaneous (SC) administration of natalizumab compared to intravenous (IV) administration as measured in the earlier EASIER study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study included: (1) time-and-motion analysis using a mobile application to collect real-world data during SC administration; (2) structured HCP questionnaire assessing organizational impacts; (3) patient survey capturing experience, preferences, and QoL. The comparison between SC and IV was conducted using a random-intercept regression model adjusted for patient history.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 265 SC procedures were analyzed. Compared to IV administration, SC reduced patient center time by 77%, HCP active time by 35%, and chair time by 74%. Hospital costs per administration decreased by 60%, with a reduction of about 33 and 14% from the perspectives of the Society and patient, respectively. Among patients, 86% preferred SC administration, mainly due to shorter center time, less physical discomfort, and lower emotional burden. QoL scores (scale 0\u2013100) were higher on SC days (mean 70.4) than IV days (mean 56.9) administration, corresponding to a 13-point improvement (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). All HCPs reported a favorable opinion on SC administration, with 82% expecting simplifications in MS center organization and shorter patient waiting lists.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>SC natalizumab administration significantly reduces dispensation procedure times, healthcare resource consumption, and associated costs, while improving patient experience and QoL.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-026-13977-w","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:42:33Z","timestamp":1783662153000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Subcutaneous natalizumab administration in relapsing\u2013remitting multiple sclerosis: results of EASIER 2 study"],"prefix":"10.1007","volume":"273","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5485-0479","authenticated-orcid":false,"given":"Massimo","family":"Filippi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi M. E.","family":"Grimaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Brescia Morra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Conte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Cordioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocco","family":"Totaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Lus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto","family":"Rini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Marinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Valentino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Perini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Girolama Alessandra","family":"Marfia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariarosaria","family":"Valente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Malucchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Zanetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Pradelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Perini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Santoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"EASIER 2 study working Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"13977_CR1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1177\/1352458512441566","volume":"18","author":"K Karampampa","year":"2012","unstructured":"Karampampa K, Gustavsson A, Miltenburger C, Eckert B (2012) Treatment experience, burden and unmet needs (TRIBUNE) in MS study: results from five European countries. Mult Scler 18:7\u201315. https:\/\/doi.org\/10.1177\/1352458512441566","journal-title":"Mult Scler"},{"key":"13977_CR2","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1177\/1352458517708176","volume":"23","author":"M Battaglia","year":"2017","unstructured":"Battaglia M, Kobelt G, Ponzio M et al (2017) New insights into the burden and costs of multiple sclerosis in Europe: results for Italy. Mult Scler 23:104\u2013116. https:\/\/doi.org\/10.1177\/1352458517708176","journal-title":"Mult Scler"},{"key":"13977_CR3","unstructured":"AIFA (2020) DETERMINA 18 novembre 2020 Introduzione della scheda cartacea per la prescrizione dei farmaci disease modifying per la sclerosi multipla per linee di trattamento successive alla prima. (Determina n. DG\/1167\/2020). (20A06440) (GU Serie Generale n.295 del 27\u201311\u20132020). https:\/\/www.gazzettaufficiale.it\/atto\/serie_generale\/caricaDettaglioAtto\/originario?atto.dataPubblicazioneGazzetta=2020-11-27&atto.codiceRedazionale=20A06440&elenco30giorni=false. Accessed 20 Mar 2025"},{"key":"13977_CR4","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1002\/ana.22247","volume":"69","author":"M Gunnarsson","year":"2011","unstructured":"Gunnarsson M, Malmestr\u00f6m C, Axelsson M et al (2011) Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab. Ann Neurol 69:83\u201389. https:\/\/doi.org\/10.1002\/ana.22247","journal-title":"Ann Neurol"},{"key":"13977_CR5","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1007\/s40265-013-0102-7","volume":"73","author":"PL McCormack","year":"2013","unstructured":"McCormack PL (2013) Natalizumab: a review of its use in the management of relapsing-remitting multiple sclerosis. Drugs 73:1463\u20131481. https:\/\/doi.org\/10.1007\/s40265-013-0102-7","journal-title":"Drugs"},{"key":"13977_CR6","unstructured":"AIFA TYSABRI 20 mg\/ml concentrato per soluzione per infusione. Riassunto delle caratteristiche del prodotto. https:\/\/medicinali.aifa.gov.it\/it\/#\/it\/dettaglio\/0000038676. Accessed 14 May 2025"},{"key":"13977_CR7","unstructured":"AIFA TYSABRI 150 mg\/ml soluzione iniettabile. Riassunto delle caratteristiche del prodotto. https:\/\/medicinali.aifa.gov.it\/it\/#\/it\/dettaglio\/0000038677. Accessed 14 May 2025"},{"key":"13977_CR8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0157957","volume":"11","author":"E De Cock","year":"2016","unstructured":"De Cock E, Kritikou P, Sandoval M et al (2016) Time savings with rituximab subcutaneous injection versus rituximab intravenous infusion: a time and motion study in eight countries. PLoS ONE 11:e0157957. https:\/\/doi.org\/10.1371\/journal.pone.0157957","journal-title":"PLoS ONE"},{"key":"13977_CR9","doi-asserted-by":"publisher","first-page":"459","DOI":"10.3111\/13696998.2014.914033","volume":"17","author":"S Rule","year":"2014","unstructured":"Rule S, Collins GP, Samanta K (2014) Subcutaneous vs intravenous rituximab in patients with non-Hodgkin lymphoma: a time-and-motion study in the United Kingdom. J Med Econ 17:459\u2013468. https:\/\/doi.org\/10.3111\/13696998.2014.914033","journal-title":"J Med Econ"},{"key":"13977_CR10","doi-asserted-by":"publisher","first-page":"227","DOI":"10.2147\/CEOR.S97319","volume":"8","author":"C Ponzetti","year":"2016","unstructured":"Ponzetti C, Canciani M, Farina M et al (2016) Potential resource and cost saving analysis of subcutaneous versus intravenous administration for rituximab in non-Hodgkin\u2019s lymphoma and for trastuzumab in breast cancer in 17 Italian hospitals based on a systematic survey. Clinicoecon Outcomes Res 8:227\u2013233. https:\/\/doi.org\/10.2147\/CEOR.S97319","journal-title":"Clinicoecon Outcomes Res"},{"key":"13977_CR11","doi-asserted-by":"publisher","first-page":"3267","DOI":"10.2217\/fon-2019-0368","volume":"15","author":"KC Anderson","year":"2019","unstructured":"Anderson KC, Landgren O, Arend RC et al (2019) Humanistic and economic impact of subcutaneous versus intravenous administration of oncology biologics. Future Oncol 15:3267\u20133281. https:\/\/doi.org\/10.2217\/fon-2019-0368","journal-title":"Future Oncol"},{"key":"13977_CR12","doi-asserted-by":"publisher","first-page":"228424031875787","DOI":"10.1177\/2284240318757871","volume":"2018","author":"A Cicchetti","year":"2018","unstructured":"Cicchetti A, Coretti S, Mascia D et al (2018) Assessing social and economic impact of subcutaneous mAbs in oncology. Glob Reg Health Technol Assess 2018:228424031875787. https:\/\/doi.org\/10.1177\/2284240318757871","journal-title":"Glob Reg Health Technol Assess"},{"key":"13977_CR13","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1007\/s00415-023-11955-0","volume":"271","author":"M Filippi","year":"2024","unstructured":"Filippi M, Grimaldi L, Conte A et al (2024) Intravenous or subcutaneous natalizumab in patients with relapsing\u2013remitting multiple sclerosis: investigation on efficiency and savings-the EASIER study. J Neurol 271:340\u2013354. https:\/\/doi.org\/10.1007\/s00415-023-11955-0","journal-title":"J Neurol"},{"key":"13977_CR14","unstructured":"ISTAT (2018) Rapporto annuale 2018. La situazione del Paese. https:\/\/www.istat.it\/storage\/rapporto-annuale\/2018\/Rapportoannuale2018.pdf. Accessed 24 Mar 2025"},{"key":"13977_CR15","doi-asserted-by":"publisher","first-page":"48","DOI":"10.33393\/ao.2024.3078","volume":"11","author":"R Bergamaschi","year":"2024","unstructured":"Bergamaschi R, Capobianco M, Ravasio R (2024) Budget impact analysis of natalizumab biosimilar on pharmaceutical expenditure for the treatment of relapsing\u2013remitting multiple sclerosis in Italy. AboutOpen 11:48\u201356. https:\/\/doi.org\/10.33393\/ao.2024.3078","journal-title":"AboutOpen"},{"key":"13977_CR16","unstructured":"ACI (2024) Costi chilometrici di esercizio. In: ACI Gov. https:\/\/aci.gov.it\/servizio\/costi-chilometrici-di-esercizio\/. Accessed 24 Mar 2025"},{"key":"13977_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.trip.2020.100200","volume":"7","author":"A Avenali","year":"2020","unstructured":"Avenali A, Catalano G, Gregori M, Matteucci G (2020) Rail versus bus local public transport services: a social cost comparison methodology. Transp Res Interdiscip Perspect 7:100200. https:\/\/doi.org\/10.1016\/j.trip.2020.100200","journal-title":"Transp Res Interdiscip Perspect"},{"key":"13977_CR18","unstructured":"Comune di Milano (2024) Servizio taxi e tariffe applicate. In: Comune di Milano. https:\/\/www.comune.milano.it\/aree-tematiche\/mobilita\/taxi. Accessed 24 Mar 2025"},{"key":"13977_CR19","unstructured":"Ebilcoba Nuovo Contratto Collettivo Nazionale di Lavoro. Colf e badanti. https:\/\/servizi2.inps.it\/docallegati\/Mig\/Allegati\/701Nuovo_CCNL_colf_badanti_Ebilcoba.pdf. Accessed 24 Mar 2025"},{"key":"13977_CR20","unstructured":"ISTAT (2019) Multiscopo sulle famiglie: uso del tempo - file per la ricerca. https:\/\/www.istat.it\/it\/archivio\/202520. Accessed 23 Nov 2022"},{"key":"13977_CR21","unstructured":"EMA Tysabri. EPAR Summary of Product Characteristics. https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/tysabri-epar-product-information_en.pdf. Accessed 10 Jul 2025"},{"key":"13977_CR22","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1007\/s40120-024-00647-0","volume":"13","author":"H Wiendl","year":"2024","unstructured":"Wiendl H, Foley J, Defer G et al (2024) Patient preference for subcutaneous versus intravenous administration with every-6-week natalizumab (Tysabri\u00ae) dosing: NOVA phase IIIb extension study (Part 2). Neurol Ther 13:1385\u20131401. https:\/\/doi.org\/10.1007\/s40120-024-00647-0","journal-title":"Neurol Ther"},{"key":"13977_CR23","doi-asserted-by":"publisher","DOI":"10.1177\/17562864241241382","volume":"17","author":"R Gold","year":"2024","unstructured":"Gold R, Schmidt S, Deisenhammer F et al (2024) Real-world evidence and patient preference for subcutaneous versus intravenous natalizumab in the treatment of relapsing\u2013remitting multiple sclerosis - initial results from the observational SISTER study. Ther Adv Neurol Disord 17:17562864241241382. https:\/\/doi.org\/10.1177\/17562864241241382","journal-title":"Ther Adv Neurol Disord"},{"key":"13977_CR24","doi-asserted-by":"publisher","first-page":"315","DOI":"10.2147\/CEOR.S501716","volume":"17","author":"L Prosperini","year":"2025","unstructured":"Prosperini L, Pradelli L, Santoni L et al (2025) Cost-minimization analysis and budget impact analysis about subcutaneous natalizumab in relapsing-remitting multiple sclerosis in Italy. Clinicoecon Outcomes Res 17:315\u2013333. https:\/\/doi.org\/10.2147\/CEOR.S501716","journal-title":"Clinicoecon Outcomes Res"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-026-13977-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-026-13977-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-026-13977-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T07:49:23Z","timestamp":1786348163000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-026-13977-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,10]]},"references-count":24,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["13977"],"URL":"https:\/\/doi.org\/10.1007\/s00415-026-13977-w","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,10]]},"assertion":[{"value":"19 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 June 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 June 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 July 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"MF: is Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Neurological Sciences, and Radiology; received compensation for consulting services from Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi; speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA; participation in Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda; scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol-Myers Squibb, Lilly, Novartis, Sanofi-Genzyme; he receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla; LMEG: has received funding for travel to attend scientific events or speaker honoraria from Merck, Biogen Idec, Sanofi-Aventis, Teva Pharmaceutical Industries Ltd., Roche, Novartis, Bayer Schering Pharma, Alexion and Neuraxpharm; VBM: disclosed travel\/meeting expenses from Novartis, Janssen, Roche and Merck and speaking honoraria from Merk, BMS, Biogen, Novartis, Roche and Almirall; AC: has served on advisory boards and\/or received honoraria for speaking or consultation fees from Biogen, Merck-Serono, Novartis, Roche, Sanofi-Genzyme, BMS, Amgen, Almirall, Alexion; CC: in the last two years I received personal compensation for advisory board, speaking and travel grants from Biogen, Novartis, Merck Serono, BMS, Roche; RT: has served on advisory boards and\/or received honoraria for speaking or consultation fees from Alexion, Almirall, Biogen, CSL behring, Janssen-Cilag, Merck-Serono, Novartis, Roche, Sanofi-Genzyme; GL: received research grants and honoraria as a speaker and member of advisory boards by: Alexion, Bristol, Bayer, Biogen Idec, Merck Serono, Novartis, Sanofi Genzyme, Almirall, Allergan, Merz, Ipsen, Roche; AR: received a grant for the organization of a scientific congress or speaker honoraria from Biogen Idec, Sanofi, Merck Serono, Bristol, and Roche; FM: received compensation for speaking activities, travel grant, and participation in advisory board from Biogen, Bristol-Myers Squibb, Novartis, Roche, Sanofi-Genzyme, and Merck-Serono; PV: has received speaker's honoraria and consulting fee, honoraria for advisory boards from Biogen Idec, Novartis, Merck Serono, Sanofi Genzyme, and TEVA; PP: has received speaker honoraria and consulting fees from Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA; GM: is an Advisory Board member of Biogen Idec, Sanofi Genzyme, Merck-Serono, Novartis, and TEVA, and received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi-Genzyme, and TEVA. She is the principal investigator in clinical trials for Actelion, Biogen Idec, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi-Genzyme, and TEVA; MV: Biogen, Sanofi, TEVA, Merck, Roche; SM: Consultation and speaking fees from Sanofi-Genzyme, Biogen-Idec, Merck Serono, Novartis, Celgene-Bristol-Myers Squibb Company, Teva; CZ: received compensation for speaking activities, and\/or consulting services, from Alexion, Astrazeneca, Biogen, Bristol-Myers Squibb, Janssen, Merck, Novartis, Roche, Sanofi; LP: is the co\u2010owner and an employee of AdRes, which has received project funding from Biogen; DP, LS: are employees of and may hold stock in Biogen.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The ethics committee of all the participating center approved the study (CET 144\u20132023 from the Comitato Etico Territoriale Lombardia 1). The study has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All persons gave their informed consent prior to their inclusion in the study.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All participating patients gave their informed consent to participate in the study.","order":3,"name":"Ethics","label":"Informed consent","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"452"}}