Relapses found to drive disability worsening in 1st years of MS

In people with relapsing forms of multiple sclerosis (MS), relapses that occur in the first few years after the disease develops have a strong impact on rates of disability worsening — but after about 2.5 years, more relapses don’t consistently result in a greater worsening of disability, according to a new study.

The findings also suggest that patients who have more disability worsening are more likely to experience relapses, and this association does not change over time.

“Relapses accrued within 2.5 years of MS onset are strong indicators of disability worsening, but late relapses accrued 2.5 years post onset are not overt risk factors for further disability worsening. In contrast, disability worsening outcomes are strong positive predictors of current and subsequent relapse risk,” the researchers wrote.

These data could be useful for predicting the course of MS, as well as guiding decisions about treatments, the scientists said.

The study, “The association between disability progression, relapses, and treatment in early relapse onset MS: an observational, multi-centre, longitudinal cohort study,” was published in Scientific Reports.

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For most people with MS, the disease is marked by relapses or flares when symptoms suddenly worsen, which intersperse periods of remission in which symptoms ease or disappear entirely.

Relapses may directly cause disability worsening when new or worsening symptoms linger even after the relapse itself has ended. But disability also can worsen independent of relapse activity.

Overall, the relationship between relapses and disability worsening over time — and how this relationship is affected by the use of disease-modifying therapies (DMTs), which target the underlying cause of the disorder — remains incompletely understood.

To learn more, a team of scientists in Australia analyzed data collected from 253 people who developed clinically isolated syndrome (CIS), which refers to a first event of MS-like symptoms. These patients were followed for up to 15 years, and during that period most (86.6%) progressed to develop clinically definitive MS.

The analysis included data on patients’ relapse activity and disability progression, as well as the use of DMTs and genetic factors that have previously been found to influence the progression of MS. The researchers constructed detailed statistical models to assess how these various factors relate to each other.

The results indicated that, in the first 2.5 years after disease onset, more relapse activity showed a strong association with worsening disability. However, at later timepoints, relapse activity did not show a clear effect on disability progression.

“Relapses predicted worsening of disability in the early years of disease activity, but their longer-term impact on disability worsening outcomes diminished significantly with time,” the researchers wrote.

In fact, data suggested that patients with more relapses at later timepoints actually may have less disability progression, though the researchers noted that this seemingly paradoxical association might be explained by patients with more relapse activity getting more aggressive DMT treatment.

Nonetheless, the scientists said that “our finding that relapses accrued 2.5 years post-onset have no effect on long-term worsening outcomes, and may in fact mitigate against them, is novel and of interest,” highlighting a need for more research to investigate these associations.

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In line with other research, the results also showed that DMT use can reduce relapse risk. Given the role of early relapses in driving disability progression, this finding “supports the commencement of DMTs during early years of disease activity,” the researchers wrote.

Whereas relapses only drove disability worsening early in the course of disease, the team’s analyses suggested that patients who experience more disability progression are also at greater risk of experiencing future relapse activity. Importantly, this association was strong at all timepoints analyzed. The connection between more disability progression and more relapse risk was not weakened by the use of DMTs.

“Disability worsening outcomes significantly contributed to relapse risk each year, and persisted over time, regardless of DMT treatments,” the scientists wrote. They added that these findings suggest “that future relapses occur as a results of the current disability worsening status, and that disability accumulation 2.5 years post-onset occurs in ways not tied to the current relapse status.”

These results, if externally validated, can be incorporated into software tools that provide vital information regarding a person’s future progression status.

Using these data and statistical models, the researchers constructed mathematical tools that could be used to predict the risk of relapse activity or worsening disability for individuals with MS.

“These results, if externally validated, can be incorporated into software tools that provide vital information regarding a person’s future progression status,” the team wrote, noting that these data also may help to guide treatment decisions.