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. 2015 May;2(5):479-91.
doi: 10.1002/acn3.187. Epub 2015 Mar 27.

Predictors of disability worsening in clinically isolated syndrome

Vilija G Jokubaitis  1 , Tim Spelman  2 , Tomas Kalincik  1 , Guillermo Izquierdo  3 , François Grand'Maison  4 , Pierre Duquette  5 , Marc Girard  5 , Alessandra Lugaresi  6 , Pierre Grammond  7 , Raymond Hupperts  8 , José Cabrera-Gomez  9 , Celia Oreja-Guevara  10 , Cavit Boz  11 , Giorgio Giuliani  12 , Ricardo Fernández-Bolaños  13 , Gerardo Iuliano  14 , Jeannette Lechner-Scott  15 , Freek Verheul  16 , Vincent van Pesch  17 , Tatjana Petkovska-Boskova  18 , Marcela Fiol  19 , Fraser Moore  20 , Edgardo Cristiano  21 , Raed Alroughani  22 , Roberto Bergamaschi  23 , Michael Barnett  24 , Mark Slee  25 , Norbert Vella  26 , Joseph Herbert  27 , Cameron Shaw  28 , Maria Laura Saladino  29 , Maria Pia Amato  30 , Danny Liew  31 , Damiano Paolicelli  32 , Helmut Butzkueven  33 , Maria Trojano  32
Affiliations

Predictors of disability worsening in clinically isolated syndrome

Vilija G Jokubaitis et al. Ann Clin Transl Neurol. 2015 May.

Abstract

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 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.

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Figures

Figure 1
Figure 1
Summary of patients analyzed in the present analysis. Note the 12-month sustained disability worsening group is a subset of the 3-month confirmed disability worsening group.
Figure 2
Figure 2
Kaplan-Meier survival curves showing proportion of patients free of 3-month confirmed and 12-month sustained disability worsening by: proportion of time on treatment (PTT; A: 3-month disability worsening; B: 12-month disability worsening) and by disease-modifying therapy (DMT) product (C:3-month disability worsening; D: 12-month disability worsening).
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