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Objective: The objective of this paper is to identify clinical or magnetic resonance imaging (MRI) predictors of longtermclinical progression in a large cohort of multiple sclerosis (MS) patients.Methods: A total of 241 relapsing–remitting (RR) MS patients were included in a nine-year follow-up (FU) study. Thereference MRIs were acquired at baseline (BL) as part of a multicenter, cross-sectional, clinical-MRI study. VolumetricMRI metrics were measured by a fully automated, operator-independent, multi-parametric segmentation method. Clinicalprogression was evaluated as defined by: conversion from RR to secondary progressive (SP) disease course; progressionof Expanded Disability Status Scale (EDSS); achievement and time to reach EDSS 4.Results: We concluded that conversion from RR to SP (OR 0.79; CI 0.7–0.9), progression of EDSS (OR 0.85; CI 0.77–0.93), achievement of EDSS 4 (OR 0.8; CI 0.7–0.9), and time to reach EDSS 4 (HR 0.88; CI 0.82–0.94) were all predictedby BL gray matter (GM) volume and, except for progression of EDSS, by BL EDSS (respectively: (OR 2.88; CI 1.9–4.36),(OR 2.7; CI 1.7–4.2), (HR 3.86; CI 1.94–7.70)).Conclusions: BL GM volume and EDSS are the best long-term predictors of disease progression in RRMS patients witha relatively long and mild disease. [ABSTRACT FROM AUTHOR] more...

OBJECTIVE: Recent findings support greater efficacy of early vs. delayed interferon beta (IFNbeta) treatment in patients with a first clinical event suggestive of multiple sclerosis (MS). We aimed to evaluate the effectiveness of early IFNbeta treatment in definite relapsing-remitting MS (RRMS) and to assess the optimal time to initiate IFNbeta treatment with regard to the greatest benefits on disability progression. METHODS: A cohort of 2,570 IFNbeta-treated RRMS patients was prospectively followed for up to 7 years in 15 Italian MS Centers. A Cox proportional hazards regression model adjusted for propensity score (PS) quintiles was used to assess differences between groups of patients with early vs. delayed IFNbeta treatment on risk of reaching a 1-point progression in the Expanded Disability Status Scale (EDSS) score, and the EDSS 4.0 and 6.0 milestones. A set of PS-adjusted Cox hazards regression models were calculated according to different times of treatment initiation (within 1 year up to within 5 years from disease onset). A sensitivity analysis was performed to assess the robustness of findings. RESULTS: The lowest hazard ratios (HRs) for the three PS quintiles-adjusted models were obtained by a cutoff of treatment initiation within 1 year from disease onset. Early treatment significantly reduced the risk of reaching a 1-point progression in EDSS score (HR = 0.63; 95% CI = 0.48-0.85; p < 0.002), and the EDSS 4.0 milestone (HR = 0.56; 95% CI = 0.36-0.90; p = 0.015). Sensitivity analysis showed the bound of significance for unmeasured confounders. INTERPRETATION: Greater benefits on disability progression may be obtained by an early IFNbeta treatment in RRMS. Ann Neurol 2009;66:513-520. [ABSTRACT FROM AUTHOR] more...