Pediatric Multiple Sclerosis: A Systematic Exploration of Effectiveness in Current and Emerging Therapeutics

Abstract

Pediatric-onset multiple sclerosis (POMS) is a rare but severe neurological condition that poses unique challenges in terms of diagnosis and treatment. With the increasing number of therapeutic options emerging in recent years, it is essential to systematically evaluate the efficacy of current and emerging treatments in the pediatric population. Objectives: This systematic review and meta-analysis aim to evaluate the efficacy of current and emerging therapeutics for pediatric MS, providing a comprehensive overview of their effectiveness and safety profiles. Methods: This systematic review was prepared using PRISMA reporting guidelines. The databases searched were PubMed, Scopus, Web of Science, and Cochrane. Risk of Bias was assessed using ROBINS-I and ROBINS-II. The GRADE approach was employed to evaluate the level of certainty in the evidence for each outcome. A meta-analysis was conducted using the Comprehensive Meta-Analysis (CMA) software. In order to identify the underlying cause of high heterogeneity, a subgroup analysis was conducted. Sensitivity analysis was checked. Results: Sixty-five studies were included in this review. Fifty-two of them enrolled in meta-analysis and the rest in qualitative synthesis. Majority of outcomes showed a moderate certainty of evidence according to the GRADE framework. Results of meta-analysis demonstrated that studies using high-efficacy therapies (HETs), notably natalizumab and ocrelizumab, showed a greater decrease in ARR with an effect size of -2.821, compared to the studies using moderate-efficacy therapies (METs) with an effect size of -2.028. A significant reduction in EDSS following administration of HETs (notably natalizumab and rituximab) was revealed. The results of univariate meta-regression demonstrated that ARR reduction following METs was significantly correlated with treatment duration.