{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T20:54:40Z","timestamp":1777582480704,"version":"3.51.4"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2018,6,14]],"date-time":"2018-06-14T00:00:00Z","timestamp":1528934400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2018,8]]},"DOI":"10.1007\/s00415-018-8916-6","type":"journal-article","created":{"date-parts":[[2018,6,14]],"date-time":"2018-06-14T07:39:06Z","timestamp":1528961946000},"page":"1850-1859","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Two-year real-life efficacy, tolerability and safety of dimethyl fumarate in an Italian multicentre study"],"prefix":"10.1007","volume":"265","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0031-9594","authenticated-orcid":false,"given":"Giulia","family":"Mallucci","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Annovazzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Miante","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Torri-Clerici","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Matta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"La Gioia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Cavarretta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Mantero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Costantini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"D\u2019Ambrosio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Zaffaroni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Ghezzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Perini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Bertolotto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. R.","family":"Rottoli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Rovaris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Balgera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Cavalla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Montomoli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Bergamaschi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,6,14]]},"reference":[{"key":"8916_CR1","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1056\/NEJMoa1206328","volume":"367","author":"RJ Fox","year":"2012","unstructured":"Fox RJ, Miller DH, Phillips JT, Hutchinson M, Havrdova E, Kita M, Yang M, Raghupathi K, Novas M, Sweetser MT, Viglietta V, Dawson KT, Investigators CS (2012) Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med 367:1087\u20131097","journal-title":"N Engl J Med"},{"key":"8916_CR2","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1056\/NEJMoa1114287","volume":"367","author":"R Gold","year":"2012","unstructured":"Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K, Tornatore C, Sweetser MT, Yang M, Sheikh SI, Dawson KT, Investigators DS (2012) Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med 367:1098\u20131107","journal-title":"N Engl J Med"},{"key":"8916_CR3","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1177\/1352458516649037","volume":"23","author":"R Gold","year":"2017","unstructured":"Gold R, Arnold DL, Bar-Or A, Hutchinson M, Kappos L, Havrdova E, MacManus DG, Yousry TA, Pozzilli C, Selmaj K, Sweetser MT, Zhang R, Yang M, Potts J, Novas M, Miller DH, Kurukulasuriya NC, Fox RJ, Phillips TJ (2017) Long-term effects of delayed-release dimethyl fumarate in multiple sclerosis: interim analysis of ENDORSE, a randomized extension study. Mult Scler 23:253\u2013265","journal-title":"Mult Scler"},{"key":"8916_CR4","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/nrneurol.2016.188","volume":"13","author":"M Trojano","year":"2017","unstructured":"Trojano M, Tintore M, Montalban X, Hillert J, Kalincik T, Iaffaldano P, Spelman T, Sormani MP, Butzkueven H (2017) Treatment decisions in multiple sclerosis\u2014insights from real-world observational studies. Nat Rev Neurol 13:105\u2013118","journal-title":"Nat Rev Neurol"},{"key":"8916_CR5","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1212\/01.WNL.0000156155.19270.F8","volume":"64","author":"RH Roxburgh","year":"2005","unstructured":"Roxburgh RH, Seaman SR, Masterman T, Hensiek AE, Sawcer SJ, Vukusic S, Achiti I, Confavreux C, Coustans M, le Page E, Edan G, McDonnell GV, Hawkins S, Trojano M, Liguori M, Cocco E, Marrosu MG, Tesser F, Leone MA, Weber A, Zipp F, Miterski B, Epplen JT, Oturai A, Sorensen PS, Celius EG, Lara NT, Montalban X, Villoslada P, Silva AM, Marta M, Leite I, Dubois B, Rubio J, Butzkueven H, Kilpatrick T, Mycko MP, Selmaj KW, Rio ME, Sa M, Salemi G, Savettieri G, Hillert J, Compston DA (2005) Multiple sclerosis severity score: using disability and disease duration to rate disease severity. Neurology 64:1144\u20131151","journal-title":"Neurology"},{"key":"8916_CR6","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1177\/1352458517703193","volume":"23","author":"G Giovannoni","year":"2017","unstructured":"Giovannoni G, Tomic D, Bright JR, Havrdova E (2017) \u201cNo evident disease activity\u201d: the use of combined assessments in the management of patients with multiple sclerosis. Mult Scler 23:1179\u20131187","journal-title":"Mult Scler"},{"issue":"Suppl 2","key":"8916_CR7","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1111\/ene.12799","volume":"22","author":"P Gallo","year":"2015","unstructured":"Gallo P, Van Wijmeersch B, Paradig MSG (2015) Overview of the management of relapsing-remitting multiple sclerosis and practical recommendations. Eur J Neurol 22(Suppl 2):14\u201321","journal-title":"Eur J Neurol"},{"key":"8916_CR8","volume-title":"Clinical measures and impact on patient-reported outcomes of delayed-release dimethyl fumarate in relapsing multiple sclerosis patients after suboptimal response to glatiramer acetate: analysis of the 12-month RESPOND study","author":"K Kresa-Reahl","year":"2016","unstructured":"Kresa-Reahl K (2016) Clinical measures and impact on patient-reported outcomes of delayed-release dimethyl fumarate in relapsing multiple sclerosis patients after suboptimal response to glatiramer acetate: analysis of the 12-month RESPOND study. ECTRIMS, ECTRIMS Online Library, London, UK"},{"key":"8916_CR9","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1007\/s00415-016-8175-3","volume":"263","author":"A Miclea","year":"2016","unstructured":"Miclea A, Leussink VI, Hartung HP, Gold R, Hoepner R (2016) Safety and efficacy of dimethyl fumarate in multiple sclerosis: a multi-center observational study. J Neurol 263:1626\u20131632","journal-title":"J Neurol"},{"key":"8916_CR10","doi-asserted-by":"publisher","first-page":"1671","DOI":"10.1016\/j.clinthera.2017.06.012","volume":"39","author":"O Fernandez","year":"2017","unstructured":"Fernandez O, Giovannoni G, Fox RJ, Gold R, Phillips JT, Potts J, Okwuokenye M, Marantz JL (2017) Efficacy and safety of delayed-release dimethyl fumarate for relapsing-remitting multiple sclerosis in prior interferon users: an integrated analysis of DEFINE and CONFIRM. Clin Ther 39:1671\u20131679","journal-title":"Clin Ther"},{"key":"8916_CR11","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1111\/ene.13272","volume":"24","author":"E Havrdova","year":"2017","unstructured":"Havrdova E, Giovannoni G, Gold R, Fox RJ, Kappos L, Phillips JT, Okwuokenye M, Marantz JL (2017) Effect of delayed-release dimethyl fumarate on no evidence of disease activity in relapsing-remitting multiple sclerosis: integrated analysis of the phase III DEFINE and CONFIRM studies. Eur J Neurol 24:726\u2013733","journal-title":"Eur J Neurol"},{"key":"8916_CR12","unstructured":"Berglund A (2016) Comparative analysis of adherence and persistence for delayed-release dimethyl fumarate versus interferons and glatiramer acetate\u2014a population based study in Sweden. In: ECTRIMS. ECTRIMS Online Library, London, UK"},{"key":"8916_CR13","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1007\/s40120-017-0080-x","volume":"6","author":"R Alroughani","year":"2017","unstructured":"Alroughani R, Ahmed SF, Behbehani R, Al-Hashel J (2017) Effectiveness and safety of dimethyl fumarate treatment in relapsing multiple sclerosis patients: real-world evidence. Neurol Ther 6:189\u2013196","journal-title":"Neurol Ther"},{"key":"8916_CR14","doi-asserted-by":"publisher","first-page":"9","DOI":"10.7224\/1537-2073.2014-101","volume":"18","author":"EJ Fox","year":"2016","unstructured":"Fox EJ, Vasquez A, Grainger W, Ma TS, von Hehn C, Walsh J, Li J, Zambrano J (2016) Gastrointestinal tolerability of delayed-release dimethyl fumarate in a multicenter, open-label study of patients with relapsing forms of multiple sclerosis (MANAGE). Int J MS Care 18:9\u201318","journal-title":"Int J MS Care"},{"key":"8916_CR15","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/j.msard.2014.03.003","volume":"3","author":"JT Phillips","year":"2014","unstructured":"Phillips JT, Hutchinson M, Fox R, Gold R, Havrdova E (2014) Managing flushing and gastrointestinal events associated with delayed-release dimethyl fumarate: experiences of an international panel. Mult Scler Relat Disord 3:513\u2013519","journal-title":"Mult Scler Relat Disord"},{"key":"8916_CR16","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/s40120-015-0037-x","volume":"4","author":"J Theodore Phillips","year":"2015","unstructured":"Theodore Phillips J, Erwin AA, Agrella S, Kremenchutzky M, Kramer JF, Darkes MJ, Kendter J, Abourjaily H, Rana J, Fox RJ (2015) Consensus management of gastrointestinal events associated with delayed-release dimethyl fumarate: a Delphi study. Neurol Ther 4:137\u2013146","journal-title":"Neurol Ther"},{"key":"8916_CR17","doi-asserted-by":"publisher","first-page":"205521731559699","DOI":"10.1177\/2055217315596994","volume":"1","author":"EE Longbrake","year":"2015","unstructured":"Longbrake EE, Naismith RT, Parks BJ, Wu GF, Cross AH (2015) Dimethyl fumarate-associated lymphopenia: risk factors and clinical significance. Mult Scler J Exp Transl Clin 1:2055217315596994. \n                    https:\/\/doi.org\/10.1177\/2055217315596994","journal-title":"Mult Scler J Exp Transl Clin"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00415-018-8916-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-018-8916-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-018-8916-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,6,13]],"date-time":"2019-06-13T19:25:43Z","timestamp":1560453943000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00415-018-8916-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,14]]},"references-count":17,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2018,8]]}},"alternative-id":["8916"],"URL":"https:\/\/doi.org\/10.1007\/s00415-018-8916-6","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,14]]},"assertion":[{"value":"7 February 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 May 2018","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 May 2018","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 June 2018","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"G. Mallucci received support to travel to scientific meetings from Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, and Teva; received speaker honoraria from Biogen Idec and served on the scientific advisory board for Genzyme and Merck Serono. P. Annovazzi received honoraria for lecturing and participation in advisory boards, and\/or travel expenses for attending congresses and meetings from Merck, Biogen, Teva, Sanofi-Genzyme, Almirall, Mylan, Roche and Novartis. S.Miante received a travel grant form Biogen Idec, Novartis, Sanofi-Aventis and Teva. V. Torri-Clerici acted as an Advisory Board member of Merck Serono, Novartis and Genzyme, and received funding for travelling and honoraria for speaking or writing or consultancy from Biogen Idec, Merck, Teva, Novartis, Genzyme, and Almirall. She received support for research project by Almirall and is involved as principal investigator in clinical trials for Novartis and Merck. M. Matta has nothing to disclose. S. La Gioia received grants from Biogen for travel and congress participation. R. Cavarretta has nothing to disclose. V. Mantero has nothing to disclose. G. Costantini has nothing to disclose. V. D\u2019Ambrosio has nothing to disclose. M. Zaffaroni received honoraria for consultancy and participation in advisory boards or travel grants from Genzyme, Biogen Idec, Merck Serono, Sanofi-Aventis, Teva, and Novartis. A. Ghezzi has served on scientific advisory boards for Merck Serono, Biogen Idec and Teva Pharmaceutical Industries Ltd; has received speaker honoraria from Merck Serono, Biogen Idec, Bayer Schering Pharma Novartis, and Serono Symposia International; served as a consultant for Novartis; and receives research support from Sanofi-Aventis, Biogen Idec and Merck Serono. P. Perini has received funding for travel and speaker honoraria from Merck Serono, Biogen Idec, Sanofi-Aventis, and Bayer Schering Pharma and has been a consultant for Merck Serono, Biogen Idec and Teva. S. Rossi acted as an Advisory Board member of Biogen Idec, Bayer Schering, Merck Serono, Teva, Novartis and Genzyme, and received funding for travelling and honoraria for speaking or writing from Biogen Idec, Merck Serono, Teva, Novartis, Bayer Schering, Genzyme, Almirall. She received support for research project by Teva, Merck Serono and Bayer Schering and is involved as principal investigator in clinical trials for Teva and Roche. A. Bertolotto served on the scientific advisory boards of Almirall, Bayer, BiogenIdec, and Genzyme; received speaker honoraria from BiogenIdec, Genzyme, Novartis, and Teva; his institution has received grant support from Bayer, BiogenIdec, Merck, Novartis, Teva, the Italian Multiple Sclerosis Society, Fondazione Ricerca Biomedica ONLUS, and San Luigi ONLUS; received speaker honoraria from BiogenIdec, Genzyme, Novartis, Sanofi-Aventis, and Teva; is on the editorial board of Multiple Sclerosis International, Progress in Neuroscience, Dataset Papers in Neuroscience, Journal of Multiple Sclerosis, Neurology and Therapy, and Multiple Sclerosis and Demyelinating Disorders; and received research support from Regione Piemonte, Italian Multiple Sclerosis Society, Associazione Ricerca Biomedica ONLUS, and San Luigi ONLUS. MR Rottoli has nothing to disclose. M. Rovaris received compensation from Biogen Italy, Teva Pharmaceuticals, Novartis, and Genzyme for speaking and consultant fees. Dr. Rovaris received financial support for research activities from Teva Pharmaceuticals and Merck Serono. R. Balgera has nothing to disclose. P. Cavalla acted as an Advisory Board member of Merck Serono and Genzyme, and received funding for travelling and honoraria for speaking or consultancy from Biogen Idec, Merck Serono, Teva, Novartis, Genzyme and Almirall. She is involved as principal investigator in clinical trials for Novartis, Biogen and Genzyme. C. Montomoli received teaching grants from Biogen Idec and Merck Serono. R. Bergamaschi received research grants from Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis and Teva received lecture honoraria from Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi-Aventis and Teva; and received support to travel to scientific meetings from Almirall, Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi-Aventis and Teva.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}]}}