Assessing response to interferon-β in a multicenter dataset of patients with MS.
OBJECTIVE
To provide new insights into the role of markers of response to interferon-β therapy in multiple sclerosis (MS) in a multicenter setting, focusing on the relevance of MRI lesions in combination with clinical variables.


METHODS
A large multicenter clinical dataset was collected within the Magnetic Resonance Imaging in MS (MAGNIMS) network. This included a large cohort of patients with relapsing-remitting MS on interferon-β treatment, MRI and clinical assessments during the first year of treatment, and clinical follow-up of at least 2 additional years. Heterogeneity among centers was assessed before pooling the data. The association of 1-year MRI or clinical relapses with the risk of treatment failure (defined as Expanded Disability Status Scale [EDSS] worsening or treatment switch for inefficacy) and of EDSS worsening alone was evaluated using multivariate Cox models.


RESULTS
A pooled dataset of 1,280 patients with relapsing-remitting MS from 9 MAGNIMS centers was analyzed. The risk of failure had a relevant increase with 1 relapse (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.39-2.44, p < 0.001) and ≥3 new T2 lesions (HR 1.55, 95% CI 0.92-2.60, p = 0.09). In patients without relapses and less than 3 new T2 lesions, the 3-year risk of failure and EDSS worsening were 17% and 15%; in patients with 1 relapse or ≥3 new T2 lesions, the risks were 27% and 22%; in patients with both conditions or more than 1 relapse, the risks were 48% (p < 0.001) and 29% (p < 0.001).


CONCLUSIONS
Substantial MRI activity, particularly if in combination with clinical relapses, during the first year of treatment with interferon-β indicates significant risk of treatment failure and EDSS worsening in the short term.
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy. mariapia.sormani@unige.it.
Maria Pia
MP
Sormani
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Claudio
C
Gasperini
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Marzia
M
Romeo
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Jordi
J
Rio
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Massimiliano
M
Calabrese
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Eleonora
E
Cocco
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Christian
C
Enzingher
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Franz
F
Fazekas
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Massimo
M
Filippi
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Antonio
A
Gallo
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Ludwig
L
Kappos
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Maria Giovanna
MG
Marrosu
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Vittorio
V
Martinelli
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Luca
L
Prosperini
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Maria Assunta
MA
Rocca
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Alex
A
Rovira
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Till
T
Sprenger
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Maria Laura
ML
Stromillo
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Gioacchino
G
Tedeschi
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Mar
M
Tintorè
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Carla
C
Tortorella
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Maria
M
Trojano
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Xavier
X
Montalban
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Carlo
C
Pozzilli
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Giancarlo
G
Comi
From the University of Genoa (M.P.S.); Hospital San Camillo Forlanini (C.G.) and Department of Neurology and Psychiatry (L.P., C.P.), Sapienza University, Rome; Department of Neurology (M.R., V.M., G.C.) and Neuroimaging Research Unit (M.A.R., M.F.), San Raffaele Scientific Institute, Milan, Italy; Hospital Universitario Vall d'Hebron (J.R., M. Tintorè, A.R., X.M.), Barcelona, Spain; University of Verona (M.C.); Department of Public Health, Clinical and Molecular Medicine (E.C.), and Department of Medical Sciences (M.G.M., E.C.), University of Cagliari, Italy; Department of Neurology (C.E., F.F.), Medical University of Graz, Austria; Dip. to di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento (A.G., G.T.), Seconda Universita' di Napoli, MRI Research Center "SUN-FISM," Hermitage-Capodimonte Clinic, Naples, Italy; Neurology (L.K., T.S.), Departments of Medicine, Clinical Research, and Biomedical Engineering, University Hospital Basel, Switzerland; DKD Helios Klinik Wiesbaden (T.S.), Germany; University of Siena (M.L.S., N.D.S.); and Department of Medical Sciences, Neurosciences and Sense Organs (M. Trojano, C.T.), University of Bari, Italy.
Nicola
N
De Stefano
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D066264:Datasets as Topic; D004185:Disability Evaluation; D005060:Europe; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000000981:diagnostic imaging / Q000188:drug therapy*; D012189:Retrospective Studies; D012306:Risk; D013997:Time Factors; D017211:Treatment Failure; D055815:Young Adult
D007155:Immunologic Factors; D016899:Interferon-beta