Résumé
Introduction: Moderately-effective therapies (MET) have been the main treatment in pediatric- onset multiple sclerosis (POMS) for years. Despite the expanding use of highly-effective therapies (HET), therapeutic guidelines for POMS are missing.Objectives/Aims: To assess the real-world effectiveness of HET as immediate treatment compared with MET on disease activity.Methods: In this retrospective observational study, we used datafrom 36 French MS expert centers participating in the Observatoire Français de la Sclérose en plaques (OFSEP), the French MS registry. We included treatment-naïve children (aged under 18 years) with relapsing-remitting MS who initiated HET or MET from 2010 to 2022. We used an innovative statistical method to model the logarithm of event rates by a penalized splines of time, allowing the possibility to model the effects of covariates in a flexible way considering non-linearity and interactions.Results: A total of 530 children were identified and met inclusion criteria (422 MET and 108 HET). Both HET and MET treatment strategies reduced the risk of first relapse within the first 2 years. HET dampened the occurrence of a first relapse with a 54% risk reduction compared to MET (adjusted Hazard Ratio HR 0.46 [95% CI 0.31-0.67]; p<0.001) and a sustained effect over 5 years of follow-up, confirmed on MRI activity (adjusted OR 0.34 [95% CI 0.18-0.66]; p=0.001) and with a better tolerability pattern. MET had six times more risk of discontinuation at 2 years (HR 5.97 [95% CI 2.92-12.20]). Index treatment was not associated with enrollment in tertiary education.Conclusion: HET as first-line strategy in POMS reduces the occurrence of a first-relapse with an optimal effect within the two first-years compared to treatment escalation, supporting a need to use immediate HET in POMS.