Starting high-efficacy monoclonal antibody therapy during childhood reduced long-term disability in pediatric-onset multiple sclerosis (MS), registry data suggested.
Among 282 patients with pediatric-onset MS, 39% started high-efficacy therapy early (at ages 12-17), and 61% started late (ages 20-22). High-efficacy therapy was defined as ocrelizumab (Ocrevus), rituximab (Rituxan), or natalizumab (Tysabri).
At ages 23-27, those who had earlier treatment had less disability, said Sifat Sharmin, PhD, of the University of Melbourne in Australia.
From baseline, the early treatment group had a mean absolute increase of 0.40 points on the Expanded Disability Status Scale (EDSS), compared with a 0.95-point increase in the late treatment group, Sharmin reported at the annual European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting in Copenhagen.
MS is “notably more active” for pediatric patients, with children experiencing two to three times more relapses than adults, Sharmin observed. “Targeting the initial highly inflammatory course in children holds promise for effectively suppressing disability progression through high-efficacy therapies,” she said.
“At present, only fingolimod [Gilenya] is approved for use in children with multiple sclerosis,” she pointed out. “However, the range of available high-efficacy therapies expands once they reach adulthood at age 18.”
In recent years, the practice of starting pediatric MS patients on more potent therapies off-label has become popular. Earlier this year, researchers in France reported that starting high-efficacy treatment in pediatric-onset MS was associated with reduced relapse risk over 5 years.
Sharmin and colleagues evaluated MS patients in the French MS Registry, Italian MS Register, and the global MSBase registry who were younger than 18 when their MS symptoms began. They included patients who started ocrelizumab, rituximab, or natalizumab treatment either between ages 12-17 or 20-22 and had follow-up until at least age 23.
The researchers estimated inverse probability treatment weights based on patients’ baseline clinical and demographic characteristics at age 18. The primary outcome was the difference in EDSS scores from baseline to ages 23-27.
In the early treatment group, about 35% were male and mean age at MS onset was 14. In the late treatment group, about 26% were male and mean MS onset age was 15. Most patients in each group were on natalizumab.
Median baseline EDSS score was 1.5 in the early group and 1.25 in the late group. Median follow-up time was 10.8 years.
Between the ages of 23 and 27, the increase in EDSS scores from baseline was 0.57 points lower in the early treatment group compared with the late treatment group (β -0.57, 95% Crl -0.90 to -0.23). Benefits of early treatment persisted throughout the follow-up period.
“The substantially lower risk of progressing to higher disability levels in the early treatment group was particularly evident in the moderate disability range, where further progression was reduced by up to 97%,” Sharmin said.
Early treatment with monoclonal antibody therapies before significant impairment emerges may be crucial for preserving neurologic function in children with MS, she noted. “Our findings indicate that initiating high-efficacy therapies like ocrelizumab, rituximab, or natalizumab during childhood can lead to significantly improved long-term outcomes, preserving neurological function and reducing disability progression,” she said.
The findings are a strong argument for rethinking current treatment guidelines, Sharmin added. “By allowing earlier access to effective treatments, we can significantly enhance the quality of life for children with MS and reduce the burden of long-term disability,” she said.
The long-term safety outcomes of starting high-efficacy treatment in children are unknown. Some treatments are being assessed in ongoing clinical trials, including the phase III OPERETTA 2 trial of ocrelizumab, noted session moderator Brenda Banwell, MD, of the Children’s Hospital of Philadelphia.
Disclosures
Sharmin reported receiving a postdoctoral fellowship from MS Australia.
Co-authors reported relationships with pharmaceutical companies and others.
Primary Source
European Committee for Treatment and Research in Multiple Sclerosis
Source Reference: Sharmin S, et al “Long-term disability outcomes among children with multiple sclerosis treated with high-efficacy therapy” ECTRIMS 2024; presentation O010/604.
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