Jokubaitis VG, Spelman T, Kalincik T, Izquierdo G, Grand'Maison F, Duquette P, Girard M, Lugaresi A, Grammond P, Hupperts R, Cabrera-Gomez J, Oreja-Guevara C, Boz C, Giuliani G, Fernández-Bolaños R, Iuliano G, Lechner-Scott J, Verheul F, van Pesch V, Petkovska-Boskova T, Fiol M, Moore F, Cristiano E, Alroughani R, Bergamaschi R, Barnett M, Slee M, Vella N, Herbert J, Shaw C, Saladino ML, Amato MP, Liew D, Paolicelli D, Butzkueven H, Trojano M. Predictors of disability worsening in clinically isolated syndrome. Ann Clin Transl Neurol.;2(5):479-91
OBJECTIVE:To assess demographic, clinical, magnetic resonance imaging, and treatment exposure predictors of time to 3 or 12-month confirmed disability worsening in clinically isolated syndrome (CIS) and early multiple sclerosis (MS).
METHODS: We utilized the MSBase Incident Study (MSBasis), a prospective cohort study of outcome after CIS. Predictors of time to first 3 and 12-month confirmed expanded disability status scale worsening were analyzed using Cox proportional hazards regression.
RESULTS: About 1989 patients were analyzed, the largest seen-from-onset cohort reported to-date. A total of 391 patients had a first 3-month confirmed disability worsening event, of which 307 were sustained for 12 months. Older age at CIS onset (adjusted hazard ratio: aHR 1.17, 95% 1.06, 1.30), pyramidal (aHR 1.45, 95% CI 1.13, 1.89) and ambulation (HR 1.60, 95% CI 1.09, 2.34) system dysfunction, annualized relapse rate (aHR 1.20, 95% CI 1.18, 1.22), and lower proportion of observation time on treatment were associated with 3-month confirmed worsening. Predictors of time to 12-month sustained worsening included pyramidal system dysfunction (Hazard ratio: aHR 1.38, 95% CI 1.05, 1.83), and older age at CIS onset (aHR 1.17, 95% CI 1.04, 1.31). Greater proportion of follow-up time exposed to treatment was associated with greater reductions in the rate of worsening.
INTERPRETATION: This study provides evidence for a strong protective effect of disease-modifying treatment to reduce disability worsening events in patients with CIS and early MS, and confirms age and pyramidal dysfunction at onset as risk factors.
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