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Aggressive multiple sclerosis (1): Towards a definition of the phenotype.

ABSTRACT: While the major phenotypes of multiple sclerosis (MS) and relapsing-remitting, primary and secondary progressive MS have been well characterized, a subgroup of patients with an active, aggressive disease course and rapid disability accumulation remains difficult to define and there is no consensus about their management and treatment. The current lack of an accepted definition and treatment guidelines for aggressive MS triggered a 2018 focused workshop of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) on aggressive MS. The aim of the workshop was to discuss approaches on how to describe and define the disease phenotype and its treatments. Unfortunately, it was not possible to come to consensus on a definition because of unavailable data correlating severe disease with imaging and molecular biomarkers. However, the workshop highlighted the need for future research needed to define this disease subtype while also focusing on its treatment and management. Here, we review previous attempts to define aggressive MS and present characteristics that might, with additional research, eventually help characterize it. A companion paper summarizes data regarding treatment and management.

SUBMITTER: Iacobaeus E

PROVIDER: S-EPMC7412876 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Aggressive multiple sclerosis (1): Towards a definition of the phenotype.

Iacobaeus Ellen E Arrambide Georgina G Amato Maria Pia MP Derfuss Tobias T Vukusic Sandra S Hemmer Bernhard B Tintore Mar M Brundin Lou L

Multiple sclerosis (Houndmills, Basingstoke, England) 20200612

While the major phenotypes of multiple sclerosis (MS) and relapsing-remitting, primary and secondary progressive MS have been well characterized, a subgroup of patients with an active, aggressive disease course and rapid disability accumulation remains difficult to define and there is no consensus about their management and treatment. The current lack of an accepted definition and treatment guidelines for aggressive MS triggered a 2018 focused workshop of the European Committee for Treatment and ...[more]

PMID: 32530385

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Project description:Currently, there are limited therapeutic options for patients with non-active secondary progressive multiple sclerosis. Therefore, real-world studies have investigated differences between patients with relapsing-remitting multiple sclerosis, non-active secondary progressive multiple sclerosis and active secondary progressive multiple sclerosis. Here, we explore patterns and predictors of transitioning between these phenotypes. We performed a cohort study using data from The Danish Multiple Sclerosis Registry. We included patients with a relapsing-remitting phenotype, registered changes to secondary progressive multiple sclerosis and subsequent transitions between relapsing and non-relapsing secondary progressive multiple sclerosis, which was defined by the presence of relapses in the previous 2 years. We analysed predictors of transitioning from relapsing-remitting multiple sclerosis to relapsing and non-relapsing secondary progressive multiple sclerosis, as well as between the secondary progressive states using a multi-state Markov model. We included 4413 patients with relapsing-remitting multiple sclerosis. Within a median follow-up of 16.2 years, 962 were diagnosed with secondary progressive multiple sclerosis by their treating physician. Of these, we classified 729 as non-relapsing and 233 as relapsing secondary progressive multiple sclerosis. The risk of transitioning from relapsing-remitting to non-relapsing secondary progressive multiple sclerosis included older age (hazard ratio per increase of 1 year in age: 1.044, 95% confidence interval: 1.035-1.053), male sex (hazard ratio for female: 0.735, 95% confidence interval: 0.619-0.874), fewer relapses (hazard ratio per each additional relapse: 0.863, 95% confidence interval: 0.823-0.906), higher expanded disability status scale (hazard ratio per each additional point: 1.522, 95% confidence interval: 1.458-1.590) and longer time on disease-modifying therapies (hazard ratio per increase of 1 year in treatment, high-efficacy disease-modifying therapy: 1.095, 95% confidence interval: 1.051-1.141; hazard ratio, moderate-efficacy disease-modifying therapy: 1.073, 95% confidence interval: 1.051-1.095). We did not find significant predictors associated with the transition from relapsing secondary progressive multiple sclerosis to non-relapsing secondary progressive multiple sclerosis, whereas older age (hazard ratio per increase of 1 year in age: 0.956, 95% confidence interval: 0.942-0.971) prevented the transition from non-relapsing secondary progressive multiple sclerosis to relapsing secondary progressive multiple sclerosis. Our study suggests that transitioning from relapsing-remitting multiple sclerosis to non-relapsing secondary progressive multiple sclerosis depends on well-known factors affecting diagnosing secondary progressive multiple sclerosis. Further transitions between non-relapsing and relapsing secondary progressive multiple sclerosis are only affected by age. These findings add to the knowledge of non-active secondary progressive multiple sclerosis, a patient group with unmet needs in terms of therapies.

Dataset Information

Aggressive multiple sclerosis (1): Towards a definition of the phenotype.

Publications

Aggressive multiple sclerosis (1): Towards a definition of the phenotype.

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