Contribution of different relapse phenotypes to disability in multiple sclerosis

Area of Science:

• Neurology
• Immunology
• Clinical Research

Background:

• Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system.
• Relapses are a hallmark of MS, contributing to neurological damage and disability accumulation.
• Understanding the impact of different relapse phenotypes on disability progression is essential for optimizing patient management.

Purpose of the Study:

• To evaluate the specific effect of various relapse phenotypes on the accumulation of disability in patients with relapse-onset multiple sclerosis.
• To identify which relapse types are most strongly associated with increased disability progression.

Main Methods:

• Analysis of prospectively collected data from 19,504 patients with relapse-onset MS from the MSBase cohort.
• Multivariable linear regression models were used to assess the association between relapse incidence, phenotype, and changes in disability (Expanded Disability Status Scale and Functional System scores).
• Minimum 1-year prospective follow-up was required, with 34,858 relapses recorded over 136,462 patient-years.

Main Results:

• Higher relapse incidence was significantly associated with greater disability accumulation (β=0.16, p<0.001).
• All relapse phenotypes contributed to disability, with pyramidal (β=0.27), cerebellar (β=0.35), and bowel/bladder (β=0.42) phenotypes showing the most pronounced effects.
• Increased incidence of specific relapse phenotypes correlated with worsening disability in corresponding and related neurological domains.

Conclusions:

• Relapses are a key driver of neurological disability accumulation in multiple sclerosis.
• Relapses involving the pyramidal, cerebellar, and bowel/bladder systems demonstrate the strongest association with disability progression.
• Preventing these specific relapse phenotypes should be a primary goal of disease-modifying therapies, potentially guiding management of treatment failure.