Many People With MS Do Not Fully Recover Post Relapse, Meta-Analysis Finds

For individuals living with multiple sclerosis (MS), relapses often leave lasting effects that may contribute to long-term disability. A new systematic review and meta-analysis found that more than one-third of people with MS did not fully recover after a relapse, with relapse severity identified as the strongest predictor of incomplete recovery.¹

Relapse severity was identified as the strongest predictor of recovery. | Image credit: © vegefox.com - stock.adobe.com

Why Understanding Relapse Recovery Matters

MS is one of the leading causes of neurological disability among young adults. Disability progression in MS can occur through 2 key pathways: relapse-associated worsening (RAW) and progression independent of relapse activity.

According to the MS Society, of 2.3 million people with MS about 1.3 million people globally have relapsing-remitting MS (RRMS).² In the UK, this disparity is even smaller, with 85% of patients with MS receiving a diagnosis for the RRMS subtype.

While disease-modifying treatments (DMTs) are effective at reducing the frequency of relapses, their ability to prevent long-term disability remains modest.¹ Researchers emphasized that relapse recovery is central to understanding how disability accumulates over time.

As the authors explained, “It is essential to gain a deeper understanding of the RAW components of MS, specifically the risk factors and biomarkers associated with incomplete recovery following relapse.” By identifying patterns in recovery, clinicians may be able to better predict which patients are most vulnerable to lasting disability.

The review followed PRISMA guidelines and included 13 studies published after 2004, representing 19,920 people with MS who experienced 27,672 relapses with at least 6 months of follow-up. Participants were mostly women, ranging from 52.8% to 80.2% of each study cohort. Mean ages also varied, with reported averages of 31.5 years in an Italian cohort, 31.6 years in a UK cohort, 34 to 35 years in several US and European cohorts, and up to 38.6 years in a smaller UK group. Most individuals had RRMS, although some studies also included people with progressive forms of the disease.

Relapses varied in presentation. Eleven studies included relapses at any neurological site, while others focused more narrowly—for example, optic neuritis or initial demyelinating events. This variability reflected the different approaches taken by researchers to define and capture relapse recovery.

What the Study Found

Across the pooled data, 42% of people with MS did not fully recover from a relapse (95% CI, 31%-54%). When limited to the 11 studies with moderate risk of bias, the rate increased to 46% (95% CI, 34%-59%).

Relapse severity was consistently the strongest predictor of incomplete recovery. In 7 of 8 studies, severe relapses were significantly associated with worse outcomes. For example, Mowry et al reported an adjusted OR of 2.38 (95% CI, 1.38-4.07; P < .01) for moderate vs mild relapses and 5.08 (95% CI, 2.42-10.69; P < .001) for severe vs mild relapses. Leone et al found an adjusted OR of 17.2 (95% CI, 2.2-136.4) for incomplete recovery following severe relapses, while Vercellino et al reported an adjusted OR of 9.59 (95% CI, 1.35-68.4).^3-5

Associations for other factors were weaker and inconsistent:¹

• Age: Some studies demonstrated that older age increased the odds of incomplete recovery; however, other studies did not find a statistically significant effect
• Sex: Male sex was sometimes associated with incomplete recovery, with ORs ranging from 1.04 to 2.28, but in several studies this effect was not statistically significant
• Disease-modifying treatment (DMT): 4 studies assessed DMT use at the time of relapse. None demonstrated a consistent link to incomplete recovery, although 2 studies reported associations with higher odds of complete recovery instead
• Disease duration: 5 studies assessed this factor; only 1 found an association with recovery outcomes, while others reported null effects
• Contrast-enhancing lesions (CELs): In 2 studies, the presence of CELs on magnetic resonance imaging did not significantly predict recovery.

The analysis was constrained by differences in study design, including variable definitions of relapse and recovery, inconsistent follow-up times, and wide variation in symptom characterization. Many participants were also not receiving DMTs at the time of relapse, which may limit the applicability of these findings to present-day MS care.

Despite these limitations, the results emphasize the need for standardized definitions of relapse severity and recovery, as well as further exploration of biomarkers that could help identify people most at risk of incomplete recovery. Preventing severe relapses remains a priority, and targeted rehabilitation or future remyelinating and neuroprotective therapies may be particularly important for those with higher risk profiles.

References

1. Ladeira F, Soares M, Faustino P, et al. Multiple sclerosis relapse incomplete recovery and associated factors – a systematic review and meta-analysis. Mult Scler Relat Disord. 2025;100:106507. doi:10.1016/j.msard.2025.106507

2. Relapsing remitting MS (RRMS). MS Society. Accessed September 3, 2025. https://www.mssociety.org.uk/about-ms/types-of-ms/relapsing-remitting-ms

3. Mowry E, Pesic M, Grimes B, Deen S, Bacchetti P, Waubant E. Demyelinating events in early multiple sclerosis have inherent severity and recovery. Neurology. 2009;72(7):602-608. doi:10.1212/01.wnl.0000342458.39625.91

4. Leone MA, Bonissoni S, Collimedaglia L, et al. Factors predicting incomplete recovery from relapses in multiple sclerosis: a prospective study. Mult Scler. 2008;14(4):485-493. doi:10.1177/1352458507084650

5. Vercellino M, Romagnolo A, Mattioda A. Multiple sclerosis relapses: a multivariable analysis of residual disability determinants. Acta Neurol Scand. 2009;119(2):126-130. doi:10.1111/j.1600-0404.2008.01076.x