Predictors of disability worsening in clinically isolated syndrome

Abstract

ObjectiveTo 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).MethodsWe 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.ResultsAbout 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.InterpretationThis 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.

The effect of oral immunomodulatory therapy on treatment uptake and persistence in multiple sclerosis

“…This highlights a need for appropriate support and counselling of women planning pregnancy to ensure that they re-engage with treatment as soon as practicable post-pregnancy to guard against disability worsening. 27 We further confirmed the findings of prior studies showing that a high EDSS score at treatment commencement is associated with treatment discontinuation. 5,8 However, here we found that relapse rate on treatment, rather than increasing EDSS score on treatment is associated with a significantly increased risk of treatment discontinuation.…”

Disease-modifying drugs can reduce disability progression in relapsing multiple sclerosis

“…In particular, in our AOMS cohort, we found that, in different quartiles of exposure, the risk reduction was related to the cumulative time spent under therapy. This adds evidence that the longer the exposure time, the more likely the protective role against a confirmed disability progression (Trojano et al, 2009;Uitdehaag et al, 2009Uitdehaag et al, , 2011Jokubaitis et al, 2015Jokubaitis et al, , 2016, which was also confirmed in sensitivity analyses. These findings are in line with those of Jokubaitis et al (2015) who found a significant benefit on 12-month CDW in patients treated for 450% of the observation period, versus 550% of the time.…”

“…This adds evidence that the longer the exposure time, the more likely the protective role against a confirmed disability progression (Trojano et al, 2009;Uitdehaag et al, 2009Uitdehaag et al, , 2011Jokubaitis et al, 2015Jokubaitis et al, , 2016, which was also confirmed in sensitivity analyses. These findings are in line with those of Jokubaitis et al (2015) who found a significant benefit on 12-month CDW in patients treated for 450% of the observation period, versus 550% of the time. Notably, we also found very similar results in our large POMS cohort (Alroughani and Boyko, 2018).…”

Characterization of annual disease progression of multiple sclerosis patients: A population-based study

“…We show that the factors age, EDSS in prior disease stage (time in state, higher prior EDSS and age at onset), progressive MS and DMD, some of which have previously found to be associated with MS disease progression when analysed in survival analyses, 1,2,10 also have significant impacts in an annual progression model.…”