Use of High-Efficacy Therapy in Children With Multiple Sclerosis to Prevent Long-Term Disability.

Abstract (English)

BACKGROUND AND OBJECTIVES: Children with multiple sclerosis (MS) are increasingly treated with high-efficacy monoclonal antibody therapies; however, treatment approaches vary widely, largely because of regulatory restrictions that often delay access until adulthood. We hypothesized that initiating these therapies during childhood confers greater benefits than their initiation in adulthood. This study, therefore, evaluated long-term disability in patients with pediatric-onset MS treated with monoclonal antibodies before age 18 compared with those who initiated these therapies in adulthood. METHODS: In this retrospective cohort study, patients younger than 18 years at the onset of MS symptoms were identified across 3 MS registries: MSBase, Observatoire Français de la Sclérose en Plaques, and the Italian MS Register. We categorized patients who commenced natalizumab, ocrelizumab, or rituximab between ages 12 and 17 into the pediatric high-efficacy therapy (HET) initiation group and those who began treatment between ages 20 and 22 into the adult HET initiation group. A landmark study design was used, with age 18 designated as the baseline and the outcome period spanning ages 23-27 years. The primary outcome was the change in Expanded Disability Status Scale (EDSS) scores, evaluated using a Bayesian weighted generalized linear mixed model. RESULTS: We included 277 patients (72% female), with a mean (SD) age at onset of MS symptoms of 14.97 (2.23) years. Of these, 108 initiated HET during childhood and 169 during adulthood. The postbaseline increase in EDSS scores was 0.53 steps lower in the pediatric HET initiation group compared with the adult group (β -0.53 [95% credible interval -0.87 to -0.19]). This benefit of pediatric HET initiation was most pronounced within the EDSS range of 4.5-6.0, with up to a 97% reduction in the odds of further disability worsening (odds ratio of EDSS score 5.0 over 4.5: 0.03 [95% credible interval 0.003-0.22]). DISCUSSION: Commencing high-efficacy monoclonal antibody therapy in childhood is associated with more favorable long-term disability outcomes than delayed initiation in adulthood. Early use of highly effective therapy is crucial for preserving neurologic function in children with MS. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, in children aged 12-17 years with MS, initiating therapy with monoclonal antibodies before age 18 (vs 20-22) is associated with less disability accrual between the ages of 23 and 27.