Disease progression independent of relapse activity (PIRA) was found to be less frequent in pediatric-onset MS than in adult-onset MS. However, even in pediatric-onset MS, PIRA accounted for about half of all confirmed disability accumulation. Early treatment with disease-modifying therapy (DMT) was effective in preventing PIRA, especially in pediatric-onset MS patients.


A real-world, multicenter, cohort study set out to compare the proportion of PIRA in pediatric-onset MS and adult-onset MS patients [1]. Extracted from the Italian MS Registry were 5,169 patients with clinically isolated syndrome and relapsing-remitting MS, assessed <1 year from onset and with follow-up of up to 5 years. They were stratified by age at onset in pediatric-onset MS (<18 years, n=323) and adult-onset MS (>18 years, n=4,846).

PIRA was less frequent in pediatric-onset MS, occurring in 22.6% of patients compared with 33.8% in adult-onset MS. PIRA accounted for 47.8% of confirmed disability accumulation events in pediatric-onset MS and 66.7% in adult-onset MS (P<0.001) during the entire follow-up of 12.2 years (P<0.001). In both cohorts, PIRA was associated with longer disease duration. A multi-variable analysis confirmed pediatric-onset MS to be a protective factor against PIRA (HR 0.665; P=0.001). Some of the most important factors associated with the risk of PIRA were:

  • Longer baseline disease duration (HR 1.574; 95% CI 1.307–1.897; P<0.001);
  • Lower baseline EDSS score (HR 0.868; 95% CI 0.832–0.905; P<0.001);
  • Lower number of relapses before the event (HR 0.62; 95% CI 0.585–0.657; P<0.001);
  • Longer follow-up spent on a DMT (HR 0.468; 95% CI 0.413–0.531; P<0.001).

In both cohorts, longer exposure to DMTs reduced the risk of PIRA and relapse-associated worsening (P<0.001). This effect was especially evident in pediatric-onset MS.

The fact that even in pediatric-onset MS, PIRA accounted for about half of all confirmed disability accumulations, suggests that MS could be considered as a continuum. Relapse-dependent disability worsening would then be interwoven with relapse-independent worsening from the very onset of MS. Dr. Emilio Portaccio (University of Florence, Italy) stressed that the demonstrated effectiveness of early treatment with DMTs, especially in pediatric-onset MS, was the most important result of the study [1]. This strategy may slow down the transition to the progressive phase of MS and reduce the long-term burden.

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