Predictors of disability worsening in clinically isolated syndrome

Vilija G. Jokubaitis*, Tim Spelman, Tomas Kalincik, Guillermo Izquierdo, Francois Grand'Maison, Pierre Duquette, Marc Girard, Alessandra Lugaresi, Pierre Grammond, Raymond Hupperts, Jose Cabrera-Gomez, Celia Oreja-Guevara, Cavit Boz, Giorgio Giuliani, Ricardo Fernandez-Bolanos, Gerardo Iuliano, Jeannette Lechner-Scott, Freek Verheul, Vincent van Pesch, Tatjana Petkovska-BoskovaMarcela Fiol, Fraser Moore, Edgardo Cristiano, Raed Alroughani, Roberto Bergamaschi, Michael Barnett, Mark Slee, Norbert Vella, Joseph Herbert, Cameron Shaw, Maria Laura Saladino, Maria Pia Amato, Danny Liew, Damiano Paolicelli, Helmut Butzkueven, Maria Trojano

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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).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.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.This study provides class IV 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.
Original languageEnglish
Pages (from-to)479-491
JournalAnnals of Clinical and Translational Neurology
Issue number5
Publication statusPublished - May 2015


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