Four distinct paths of disability progression emerge in relapsing MS
Findings may help explain why symptoms worsen even without relapses
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- Disability progression in relapsing MS follows four patterns: minimal, late, early, or rapid worsening.
- Progression independent of relapse activity (PIRA) was the main driver of disability worsening across all groups.
- Disease-modifying therapies, especially high-efficacy drugs, were associated with less disability progression.
Disability progression in relapsing forms of multiple sclerosis (MS) tends to follow one of four distinct patterns, according to long-term data from more than 5,000 people with relapsing-onset MS followed in an Italian registry.
The study specifically found that disability progression could generally be categorized into four patterns: minimal-worsening, late-worsening, early-worsening, and rapid-worsening.
Although all patients had relapsing forms of MS, progression independent of relapse activity, or PIRA, emerged as the main driver of disability progression across all groups. Treatment with disease-modifying therapies (DMTs) significantly reduced disability accumulation, with some groups benefiting particularly from high-efficacy drugs.
The study, “Disability Worsening Phenotypes in Multiple Sclerosis and Impact of Disease-Modifying Treatments,” was published in Neurology.
What relapsing MS looks like and how disability can build over time
Relapsing forms of MS are marked by periods of acute symptom worsening, called relapses, followed by periods of remission when symptoms ease. Sometimes, symptoms linger after a relapse and contribute to permanent disability.
While relapses were thought to be the main driver of disability progression in relapsing MS, growing evidence suggests that many patients also experience worsening disability in periods outside relapses — known as progression independent of relapse activity (PIRA).
To better understand patterns of disability progression in relapsing MS and their main drivers, researchers in Italy examined data from 2,563 patients who were not receiving DMTs.
They found that most patients (70%) followed a late-worsening pattern, marked by low disability levels for about the first 10 years, followed by later disability progression.
A small proportion of patients (3%) showed an early-worsening pattern, with relatively low disability in the first five years followed by rapid progression.
Another 15% followed a minimal-worsening pattern, marked by very slow disability progression over the first 10 years, with disability levels remaining low and stabilizing around an Expanded Disability Status Scale (EDSS) score of 2, which reflects minimal disability.
The remaining 12% followed a rapid-worsening pattern, with disability scores increasing quickly in the years soon after MS onset.
The researchers found that people with minimal-worsening and late-worsening patterns tended to be younger and have less severe disability at disease onset compared with those in the other two groups.
Additionally, optic neuritis — inflammation in the nerve connecting the eye to the brain that can cause vision problems — was more common at onset in patients who later experienced the late-worsening pattern.
Brain scans reveal clues linked to different disability paths
MRI features linked to the four patterns were also identified. For example, patients with the early-worsening pattern more often had actively inflamed lesions on MRI scans performed soon after disease onset, while those with the rapid-worsening pattern more frequently had nine or more lesions on initial scans.
The rapid-worsening group also had a higher relapse rate, and a greater proportion of these patients experienced relapse-associated worsening. Even so, PIRA was found to be the main driver of worsening disability across all four patterns.
“PIRA was the primary driver of disability worsening across all newly defined [patterns], with no statistically significant differences between them,” the researchers wrote.
Using data from 2,952 patients treated with DMTs, the researchers then assessed how treatment was associated with disability trajectories. In this group, 61% showed late-worsening, 18% minimal-worsening, 13% early-worsening, and 8% rapid-worsening.
The data showed that higher-efficacy therapies were generally associated with less disability accumulation across all groups, including among patients with minimal disability.
“Clinically, these phenotypes may aid personalized treatment selection and monitoring, provided adequate validation; in research, they represent a potentially useful framework for studying disability progression and treatment response,” the researchers wrote.
