PIRA in Children With MS: Early Disease-Modifying Therapy May Offer Protection

Compared with individuals with adult- or late-onset multiple sclerosis (MS), children with MS are less likely to exhibit progression independent of relapse activity (PIRA) or relapse-associated worsening over a decade of follow-up. However, beginning in young adulthood, PIRA does increase rapidly in this patient population. These are the findings of a study published in JAMA Neurology. 

Researchers in Italy conducted a prospective, multicenter, cohort study from June 1, 2000 to September 30, 2021. They collected data on 16,130 patients with MS (median age, 28.7; 68.3% female) from the Italian MS register (IMSR). Of these 16,130 patients, 1383 (median age at onset, 15.8) were diagnosed with pediatric-onset MS, while 14,113 were diagnosed as having adult-onset MS (median age at onset, 29.3) and the remaining 634 had late-onset MS.

Outcomes of interest included PIRA and relapse-associated worsening. PIRA is defined as having an event leading to confirmed disability accrual scores that occurred more than 90 days after and more than 30 days prior to a relapse. Accrual of disability was determined if an increase in Expanded Disability Status Scale (EDSS) scores lasting 48 weeks or longer compared to baseline measurement. In contrast, relapse-associated worsening occurred within 90 days of a relapse or 30 days prior to a relapse.

PIRA occurred in 7176 individuals (44.5%) — 558 in the pediatric-onset MS group, 6258 in the adult-onset MS group, and 360 in the late-onset MS group. Risk for MS PIRA increased with increasing age from:

• 1.3% at age 20,
• 9% between ages 21 and 30,
• 21.6% at age 40,
• 39% at age 50,
• 61% at age 60, and
• 78.7% at age 70.

Incidence of relapse-associated worsening events also increased as age increased.

Compared to the other 2 subgroups with MS, those with pediatric-onset MS exhibited less disability based on EDSS scores, more active disease, and longer exposure to DMT. They were also less likely to experience PIRA, which was more likely in individuals who were older at MS onset (adult- vs pediatric-onset MS: hazard ratio [HR], 1.42; 95% CI, 1.30-1.55; P <.001; late- vs pediatric-onset MS: HR, 2.98; 95% CI, 2.60-3.41; P <.001).

In addition to older age, other factors associated with increased risk for PIRA included longer disease duration (HR, 1.04; 95% CI, 1.04-1.05; P <.001) and shorter exposure to DMT (HR, 0.69; 95% CI, 0.66-0.74; P <.001).

Delayed initiation of DMT also corresponded to a higher risk for experiencing both PIRA (HR, 1.75; 95% CI, 1.28-2.39; P =.001) and relapse-associated worsening (HR, 1.16; 95% CI, 1.00-1.34; P =.04).

“PIRA can occur at any age, and although pediatric onset is not fully protective against progression, this study’s findings suggest that patients with pediatric onset are less likely to exhibit PIRA over a decade of follow-up,” the researchers concluded. “However, these data also reinforce the benefit for DMT initiation in patients with POMS [pediatric onset MS], as treatment was associated with reduced occurrence of both PIRA and RAW [relapse-associated worsening] regardless of age at onset.”

Study limitations included solely using the EDSS to define confirmed disability accrual events and potential underestimation of events indicating PIRA.

Disclosures: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see original source for full list of disclosures.