Maria Pia Sormani1, Claudio Gasperini2, Marzia Romeo2, Jordi Rio2, Massimiliano Calabrese2, Eleonora Cocco2, Christian Enzingher2, Franz Fazekas2, Massimo Filippi2, Antonio Gallo2, Ludwig Kappos2, Maria Giovanna Marrosu2, Vittorio Martinelli2, Luca Prosperini2, Maria Assunta Rocca2, Alex Rovira2, Till Sprenger2, Maria Laura Stromillo2, Gioacchino Tedeschi2, Mar Tintorè2, Carla Tortorella2, Maria Trojano2, Xavier Montalban2, Carlo Pozzilli2, Giancarlo Comi2, Nicola De Stefano2. 1. 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. 2. 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.
Abstract
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.
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.
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