This study, conducted by the Observatoire Français de la Sclérose en Plaques (OFSEP), aimed to assess the effectiveness of highly effective therapies (HETs) compared to moderately effective therapies (METs) as first-line treatments for pediatric-onset multiple sclerosis (POMS). The study included 530 children with POMS who initiated treatment between 2010 and 2022, with a median follow-up of 5.8 years. The primary outcome was the time to the first relapse, while secondary outcomes included annualized relapse rate (ARR), magnetic resonance imaging (MRI) activity, time to Expanded Disability Status Scale (EDSS) progression, tertiary education attainment, and treatment safety/tolerability. Key findings include: - Both HET and MET reduced the risk of the first relapse within the first 2 years, but HET showed a more significant reduction (54% lower risk) over 5 years. - HET was associated with a 91.6% reduction in ARR compared to 74.0% for MET. - HET was associated with a 66% reduction in MRI activity at 2 years. - Treatment discontinuation rates were higher for MET (5.97 times higher) compared to HET. - HET was associated with better tolerability and fewer treatment switches. - No significant differences were found in EDSS progression or tertiary education attainment between the two groups. The study suggests that HET should be prioritized as the initial treatment strategy for POMS, although long-term safety studies are still needed. The findings support the current expert opinions and highlight the importance of early and effective treatment in managing POMS.This study, conducted by the Observatoire Français de la Sclérose en Plaques (OFSEP), aimed to assess the effectiveness of highly effective therapies (HETs) compared to moderately effective therapies (METs) as first-line treatments for pediatric-onset multiple sclerosis (POMS). The study included 530 children with POMS who initiated treatment between 2010 and 2022, with a median follow-up of 5.8 years. The primary outcome was the time to the first relapse, while secondary outcomes included annualized relapse rate (ARR), magnetic resonance imaging (MRI) activity, time to Expanded Disability Status Scale (EDSS) progression, tertiary education attainment, and treatment safety/tolerability. Key findings include: - Both HET and MET reduced the risk of the first relapse within the first 2 years, but HET showed a more significant reduction (54% lower risk) over 5 years. - HET was associated with a 91.6% reduction in ARR compared to 74.0% for MET. - HET was associated with a 66% reduction in MRI activity at 2 years. - Treatment discontinuation rates were higher for MET (5.97 times higher) compared to HET. - HET was associated with better tolerability and fewer treatment switches. - No significant differences were found in EDSS progression or tertiary education attainment between the two groups. The study suggests that HET should be prioritized as the initial treatment strategy for POMS, although long-term safety studies are still needed. The findings support the current expert opinions and highlight the importance of early and effective treatment in managing POMS.