The authors declare that they have no competing interests in relation to this work. Potential conflicts of interest outside the submitted work are as follows: M. Filippi 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, 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; E. Pagani has nothing to disclose; R. Turrini is a Novartis full employee; M. Bartezaghi is a Novartis full employee; V. Brescia Morra has received research grants from FISM Federazione Italiana Sclerosi Multipla and Roche, honoraria from Allergan, Biogen, BMS Celgene, Ipsen, Merck, Novartis, Sanofi-Genzyme, and Roche; G. Borriello received compensation for travel grants and consulting fee for advisory board and/or speaking activities from Almirall, Biogen, BMS, Janssen, Merck Serono, Novartis, Sanofi and Roche; V. Torri Clerici received honoraria for speaking or writing from Novartis, Sanofi-Genzyme, Almirall, Bristol Meyer Squibb and Horizon, she acted as an Advisory Board member for Biogen, Novartis, Sanofi-Genzyme, Bristol Meyer Squibb, Roche, Almirall, Lundbeck and Merck-Serono, she is involved as principal investigator in clinical trials for Sanofi-Genzyme, FISM, Bristol Meyer Squibb, Roche and Merck-Serono, she has received support for research projects from Almirall; Massimiliano Mirabella reports scientific advisory board membership with Bayer Schering, Biogen, Sanofi-Genzyme, Merck, Novartis, Roche, consulting and/or speaking fees, research support or travel grants from Almirall, Alexion, Bayer Schering, Bristol-Myers-Squibb, Biogen, Janssen, Sanofi-Genzyme, Merck, Novartis, Roche, Viatris, he was principal investigator in clinical trials for Argenx, Biogen, CSL Behring, Merck, Novartis, Roche, Sanofi Genzyme, Teva, Ultragenix; L. Pasquali received personal compensation for travel and participation in speaking activities by Alexion, Biogen, Sanofi, Merck, Novartis, Roche; F. Patti received speaker honoraria or advisory board fees from Almirall, Bayer, Biogen, Celgene, Merck, Myalin, Novartis, Roche, Sanofi-Genzyme and TEVA, he received research funding from Ministero Italiano della Università e della Ricerca Scientifica, Fondazione Italiana Sclerosi Multipla, Biogen and Merck; R. Totaro has served on advisory boards and/or received honoraria for speaking or consultation fees from Biogen, Merck-Serono, Novartis, Roche, Sanofi-Genzyme, and Teva; P. Gallo reports grants from Almirall, Teva, Sanofi Genzyme, Merck Serono, Biogen Italy, Novartis, Roche and Bristol Myers Squibb, consultancies for Novartis, Biogen Italy, Sanofi Genzyme, Roche and Bristol Myers Squibb, board membership Sanofi Genzyme, Novartis, Biogen Italy, Roche, Merck Serono and Bristol Myers Squibb; M.A. Rocca received consulting fees from Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche, speaker honoraria from AstraZaneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva, she receives research support from the MS Society of Canada, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla, she is Associate Editor for Multiple Sclerosis and Related Disorders.

Coinvestigators (disclosures not needed): S. Galgani received fees as invited speaker or travel expenses for attending meeting from Biogen, Merck‐Serono, Teva, Almirall, Sanofi‐Aventis, Novartis, and Genzyme. D. Maimone reported receiving personal fees from Biogen, Merck, Novartis, Roche, Sanofi, and Bristol-Myers Squibb. M. Danni has nothing to disclose. P. Valentino has nothing to disclose. M. Calabrese reported grants from Novartis, Roche, Sanofi, and Biogen outside the submitted work. M. G. Piscaglia has nothing to disclose. M. Trojano reported receiving personal fees from Biogen, Novartis, Roche, Merck, Bristol Meyer Squibb, and Genzyme and grants from Biogen, Novartis, and Roche outside the submitted work. K. Plewnia has nothing to disclose. M. Zaffaroni has nothing to disclose. M. Onofrj has nothing to disclose. D. Centonze has nothing to disclose. P. Cavalla received honoraria for consultancy or speaking from Alexion, Biogen, BMS, Merck, Novartis, Sanofi, Roche. P. Banfi has nothing to disclose. M. Pizzorno has nothing to disclose. R. Bergamaschi reported receiving grants from Biogen, Merck Serono, Roche, Novartis, and Sanofi Genzyme and personal fees from Biogen, Merck Serono, Roche, Novartis, Celgene, Janssen, and Sanofi Genzyme outside the submitted work. M. Rovaris has nothing to disclose. V. Barcella has nothing to disclose. E. Ferraro has nothing to disclose. G. Meola has nothing to disclose. E. Cocco has nothing to disclose.

The protocol was approved by the Independent Ethics Committee or Institutional Review Board at each Italian center involved in the study. Written informed consent was obtained from all patients or from a legal representative of the patient, prior to study participation any study assessment according to the Declaration of Helsinki.