Treatment Improvements for Pediatric-Onset MS Have Reduced Risk of Persistent Disability

Disease Spotlight | <b>Disease Spotlight: Multiple Sclerosis</b>

Improvements in DMTs and management standards appear to have lowered the risk of progression to EDSS scores of 4.0 and 6.0 for those with pediatric-onset disease.

A recently published study’s findings suggest that the improvements in disease-modifying therapeutics (DMTs) and management standards have led to the reduction of the risk of persistent disability for individuals with pediatric-onset multiple sclerosis (MS) by 50% to 70%. The results imply that an increase in approved DMTs prior to age 18 and continuous upgrades to management tactics can further advance prognosis for this patient population.

In a cohort of more than 3100 patients with pediatric-onset disease, the cumulative risk of reaching disability milestones decreased gradually over time for Expanded Disability Status Scale (EDSS) scores of both 4.0— implying significant disability but self-sufficiency and an ability to be up and about for about 12 hours per day— and 6.0—implying the requirement of a walking aid such as a cane or crutch. The hazard ratios (HRs) of these milestones were compared between pre-1993 and the time periods of 1993-1999, 2000-2006, and 2007-2013.

“The gradual decrease of disability risk corresponded to an increased use of DMTs over time, especially the most efficacious (ie, natalizumab and fingolimod), while disease activity at onset did not change significantly. Moreover, in recent diagnosis epochs, patients with [pediatric-onset] MS started earlier and continued taking DMTs longer compared with the past,” the study authors, including Pietro Iaffaldano, MD, assistant professor of neurology, University of Bari Aldo Moro, concluded. “Based on these results, our hypothesis is that improvement of [pediatric-onset] MS prognosis probably depends on changing therapeutic standards in MS.”

Iaddaldano and colleagues added that patients with pediatric diagnosis (n = 1300; 41% of the total cohort), who were the most active and early treated, had a lower HR for reaching EDSS of at least 4.0 in the most recent diagnosis epoch of 2007-2013 (HR, 0.35; 95% CI, 0.19-0.63).

All told, though, the median survival time to reach EDSS of at least 4.0 and at least 6.0 was lower for patients with pediatric diagnosis (EDSS 4.0: 27.8 years [95% CI, 25.7-29.8]; EDSS 6.0: 35.2 years [95% CI, 31.7-38.6]) than those with adult diagnosis (EDSS 4.0: 32.8 years [95% CI, 31.7-33.8]; EDSS 6.0: 41.1 years [95% CI, 38.8-43.2]), a difference which was statistically significant (P <.001 for both).

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“Similar to the overall cohort, the risk of reaching disability milestones decreased over time for EDSS scores of at least 4.0 in the adjusted Cox model. However, for EDSS scores of at least 6.0, the latest diagnosis epoch (2007-2013) did not reach statistical significance, but the number of events was very low,” Iaddaldano et al. wrote.

The percentage of patients starting DMTs in pediatric age was higher than the rest of the cohort (53% vs 1%; P < .001), and it significantly increased over time (12%, 32%, 66%, and 79% in <1993, 1993-1999, 2000-2006, and 2007-2013, respectively; P < .001).

The full study cohort included 3198 patients (69% female) with a mean age of disease onset of 15.2 years and a median time to diagnosis of 3.2 years, and a mean follow-up of 21.8 years (standard deviation [SD], 11.7). The annualized relapse rate (ARR) in the first year was 1.3 and in the first 3 years was 0.6, and median survival times to reach EDSS score of 4.0 and 6.0 were 31.7 years (95% CI, 30.6-32.7) and 40.5 years (95% CI, 38.6-42.4), respectively.

The distribution of patients among the assessed diagnosis epochs was 259 (20%) pre-1993, 259 (20%) from 1993-1999, 368 (28%) from 2000 to 2006, and 414 (32%) from 2007 to 2013. Data were extracted and collected in May 2019 from the Italian MS Registry, a digital database including more than 59 000 patients.

The cumulative risk of reaching disability milestones gradually decreased for EDSS with the following HRs for the 3 comparative time periods:

  • EDSS 4.0
    • 1993-1999: HR, 0.70 (95% CI, 0.58-0.83)
    • 2000-2006: HR, 0.48 (95% CI, 0.38-0.60)
    • 2007-2013: HR, 0.44 (95% CI, 0.32-0.59)
  • EDSS 6.0
    • 1993-1999: HR, 0.72 (95% CI, 0.57-0.90)
    • 2000-2006: HR, 0.44 (95% CI, 0.33-0.60)
    • 2007-2013: HR, 0.30 (95% CI, 0.20-0.46)

“In later diagnosis epochs, a greater number of patients with [pediatric-onset] MS were treated with DMTs, especially high-potency drugs, that were given earlier and for a longer period. Demographic characteristics and clinical disease activity at onset did not change significantly over time,” Iaffaldano et al. wrote.

Baroncini D, Simon M, Iaffaldano P, et al. Risk of Persistent Disability in Patients With Pediatric-Onset Multiple Sclerosis. JAMA Neurol. Published online May 3, 2021. doi:10.1001/jamaneurol.2021.1008.