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Pediatric-onset multiple sclerosis (MS) patients showed progression independent of relapse activity (PIRA) even when they were relatively young, a prospective cohort study found.

Confirmed PIRA events within 48 weeks of baseline occurred in 40.4% of pediatric-onset MS patients and were more frequent in older-onset groups, reported Maria Pia Amato, MD, of the University of Florence in Italy, and co-authors in .

For a subgroup of MS patients with at least one (EDSS) evaluation every 6 months, the incidence of PIRA was 1.3% at age 20 but rapidly increased to 9% from ages 21 through 30, then nearly doubled with each additional age decade from ages 40 to 70. Cumulative relapse-associated worsening (RAW) followed a similar trend from ages 20 to 60.

While MS patients younger than 18 have a lower rate of disability, pediatric age itself is not protective, Amato and colleagues observed. "In other words, the time of injury itself is not protective against disability; rather, while the subject has a youthful immune system and a more resilient brain, less disability is manifest," they wrote.

PIRA, especially when it develops early in MS, is a dominant driver of over time. Prior research suggested that for PIRA because of its prominence in older patients, but information about the relative contributions of PIRA and RAW to disability accrual in pediatric-onset MS is scarce.

"We ... hypothesized that, in this young population, the main driver of disability accumulation had to be RAW," Amato wrote in an email to 番茄社区, but "our hypothesis was only partially met."

"Early and accurate diagnosis and early treatment are essential in pediatric-onset MS patients, as they are at risk of irreversible disability accrual while they are still very young," she added.

The findings provide "further confirmation that risk of disease progression in pediatric-onset MS is high, and that earlier treatment and anti-inflammatory therapy confers long term benefits in this population, including benefits related to progression," noted Ann Yeh, MD, of the Hospital for Sick Children in Toronto, who wasn't involved with the study.

"Importantly, progression may occur at a relatively young age even in the absence of clinical relapses," Yeh told 番茄社区.

Amato and colleagues used data from the from 2000 to 2021. They included 16,130 MS patients with clinically isolated syndrome and relapsing-remitting course at first neurologic evaluation who subsequently had three or more EDSS evaluations and 5 years or more of follow-up. Patients with a primary or secondary progressive course at first evaluation and those enrolled in clinical trials were excluded.

Three age groups of MS patients were evaluated: pediatric-onset (age 18 or younger when diagnosed), adult-onset (ages 19-50), and late-onset patients (older than 50). The overall cohort had a median age of 28.7 at disease onset and was 68.3% female. The pediatric-onset group had a median age of 15.8 at onset and also was 68.3% female.

Baseline was defined as the first EDSS evaluation, and follow-up time was the time between the first and last available EDSS entry. Confirmed disability accrual (CDA) was a confirmed disability increase of a number of points (depending on baseline score) on the EDSS 48 weeks or more from baseline.

RAW was defined as a CDA event in which the increase in disability happened either 90 days or earlier after a relapse, or 30 days or earlier before relapse. PIRA was defined as a CDA event occurring more than 90 days after a relapse, or more than 30 days before relapse.

A first 48-week CDA event occurred in 55.2% of patients. PIRA accounted for 74.4% of CDA events that occurred in pediatric-onset MS, 80.8% of those occurring in adult-onset MS, and 90.5% of those seen in late-onset MS.

Overall, 94.2% of participants received moderate-efficacy disease-modifying therapy (DMT) and 5.8% received high-efficacy DMT. Older age at onset (adult-onset MS vs pediatric-onset HR 1.42; late-onset MS vs pediatric-onset HR 2.98), longer disease duration (HR 1.04), and shorter exposure to DMT (HR 0.69) were associated with PIRA (all P<0.001).

Limitations included a definition of CDA based on EDSS scores. MRI data within 2 years of PIRA were available for only 68% of participants, but factors associated with PIRA in this group were comparable to those in the entire cohort, the researchers noted.

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