Multiple Sclerosis Disability Evolution Risk Profile Informs Personalized Treatment

Valentina Tomassini, MD, PhD, a clinical senior lecturer in the Division of Psychological Medicine and Clinical Neurosciences at the Cardiff University School of Medicine

Valentina Tomassini, MD, PhD

According to the findings of a real-world clinical analysis, increasing disability in patients with multiple sclerosis (MS) has been found to be associated with persistent disease activity, with age predicting disability in absence of activity.

The presence of both factors increased the risk of developing severe disability. Additionally, a high number of relapses was found to aid in early identification of worsening in the presence of disease activity. Ultimately, in patients with disease activity, the number of relapses before reaching Expanded Disability Status Scale (EDSS) scores of 3.0 to 4.0 predicted increasing disability, while age >45 years at baseline predicted increasing disability sans disease activity. Combining age and the number of relapses increased the risk of and shortened the time to an EDSS score of 6.0.

Led by Valentina Tomassini, MD, PhD, a clinical senior lecturer in the Division of Psychological Medicine and Clinical Neurosciences at the Cardiff University School of Medicine, the investigators examined demographic, clinical, and magnetic resonance imaging (MRI) data from 542 patients with relapsing MS, in order to determine the profiles of disability evolution, identify early predictors, and develop risk scores for increasing disability.

The risk scores were defined as follows:

1. Score = 0, if the patient was ≤45 years and experienced ≤6 relapses before reaching an EDSS of 3.0 to 4.0.
2. Score = 1, if the patient was >45 years or, alternatively, experienced >6 relapses before reaching an EDSS of 3.0 to 4.0.
3. Score = 2, if the patient was >45 years and experienced >6 relapses before reaching an EDSS of 0 to 4.0.

Of the patients in the study cohort, 48% (n = 259) of patients had a score of 0, 41.7% (n = 226) had a score of 1, and 10% (n = 57) had a score of 2. An increase in the risk score led to an increased probability of reaching EDSS ≥6.0 (P = .001). The chance of reaching an EDSS score of ≥6.0 was 56% for those with a score of 0, 68% for those with a score of 1 (HR, 1.52; P = .001), and 75% for those with a score of 2 (HR, 2.22; P <.001).

Tomassini and colleagues wrote that “despite clinical heterogeneity in the course of MS, more inflammatory versus more degenerative evolutions can be identified by specific patterns of MS damage. Also, at a given time point along the course of the disease, these patterns are homogeneous within the same patient, thus making the identification of individual disability profiles possible, as well as relevant for therapeutic implications.”

In total, 63% (n = 344) of patients reached an EDSS score of ≥6.0, compared to the remaining 37% (n = 198) did not. Of the 344 experiencing an increase in disability, 36% (Group C; n = 124) showed no disease activity while 64% (Group D; n = 220) did. Of those not experiencing disability increases, 42% (Group A; n = 84) showed no disease activity and 58% (Group B; n = 114) did.

The group with increasing disability, mean number of years to reach EDSS ≥6.0 from an EDSS of 3.0 to 4.0 was 6.4 ±2.8 years, compared to 6.4 ±3.3 years in the group without increasing disability (P = .24).

The risk of reaching the disability outcome was higher for patients >45 (hazard ratio [HR], 1.31; P = .04), as well as in those who experienced >6 relapses before an EDSS of 3.0 to 4.0 (HR, 1.32; P = .03). Tomassini and colleagues noted that for those with disease activity, the only predictor of the ensuing confirmed increase in disability was experiencing >6 relapses prior to reaching EDSS 3.0 to 4.0 (HR, 1.53; P = .009).

The presence of disease-modifying therapies did not impact the attainment of EDSS ≥6.0, though those administered high-efficacy therapies at the time of EDSS 3.0 to 4.0 were associated with a lower proportion of increased disability during the study. Of the patients taking either interferon ß or glatiramer acetate, 66% (n = 234) had increasing disability, compared to 64% (n = 60) of those on immunosuppressants. Meanwhile, 52% (n = 50) of those taking natalizumab experienced increasing disability (P = .03).

The investigators concluded that the findings help meet the need for early recognition of disease trajectories and imply that appropriate treatment interventions in the window of opportunity can prevent or delay disability evolution and that disease activity should be treated regardless of disability at presentation. “Quantifying the individual risk of disability attainment and describing the profile of clinical worsening can aid the development of personalized approaches to MS treatment,” they wrote.

REFERENCE

Tomassini V, Fanelli F, Prosperini L, et al. Predicting the profile of increasing disability in multiple sclerosis. Mult Scler J. Epub 2018. doi: 10.1177/1352458518790397.