Predicting the profile of increasing disability in multiple sclerosis

Abstract

Background: Effective therapeutic strategies to preserve function and delay progression in multiple sclerosis (MS) require early recognition of individual disease trajectories.

Objectives: To determine the profiles of disability evolution, identify their early predictors and develop a risk score of increasing disability.

Methods: We analysed demographic, clinical and magnetic resonance imaging (MRI) data from patients with relapsing MS, Expanded Disability Status Scale (EDSS) score of 3.0-4.0 and follow-up ≥ 2 years. Attaining EDSS = 6.0 defined increasing disability; relapses and/or MRI defined disease activity.

Results: In total, 344 out of 542 (63.5%) patients reached EDSS ≥ 6.0; of these, 220 (64.0%) showed disease activity. In patients with activity, the number of relapses before reaching EDSS 3.0-4.0 predicted increasing disability; age > 45 at baseline predicted increasing disability without activity. Combining age and number of relapses increased the risk of and shortened the time to EDSS = 6.0.

Conclusion: Increasing disability is frequently associated with persistent activity. The high number of relapses identifies early those patients worsening in the presence of activity. Age predicts increasing disability in the absence of activity. The presence of both factors increases the risk of developing severe disability. As this study likely describes the transition to progression, our findings contribute to improving patient management and stratification in trials on progressive MS.

Keywords: MRI; Multiple sclerosis; age; disability; predictors; relapse.

Figure 1.

MS patients reaching the outcome (EDSS ≥ 6.0) or ending the follow-up before attaining it. Disease activity was defined as the occurrence of relapses or enhancing lesions on the MRI scan. Over a mean ± SD observation period of 6.3 ± 3.1 years, the majority of patients attained an EDSS ≥ 6.0, mainly in association with disease activity. The four groups defined by the attainment of the disability outcome in the presence or absence of disease activity are indicated as groups A, B, C and D.

Figure 2.

Kaplan–Meier curves for profiles of increasing disability in MS patients. A composite risk score is shown of increasing disability that includes age at the time of EDSS 3.0–4.0 and number of relapses before attaining EDSS 3.0–4.0 as significant predictors of clinical evolution. Risk indicates the proportion of patients who reached the disability outcome in each scoring group. Hazard ratio (HR) indicates the risk of reaching the disability outcome with respect to the reference group of patients with age ≤ 45 years and ≤6 relapses. An increase in the risk score leads to a significantly increased probability of reaching the disability outcome.