Disease-modifying Therapy In Pediatric Multiple Sclerosis: A Descriptive Systematic Review

Background:It has been recognized that multiple sclerosis (MS) can attack childrenand adolescents, whose clinical characteristics is different from adultpatients’. The research on therapies of these patients is insufficient, so thatthe interventions during disease remission are limited. The treatments usedin adult patients with MS had been used in pediatric patients in some studies,but its efficacy and safety have to be considered. This paper aims to evaluatethe efficacy and safety of diseases-modifing therapy (DMT) for children andadolescents by systematic review, in order to provide a theoretical basis forclinical application.Objective:To systematic review the efficacy and safety of the DMT in pediatricMS patients.Methods:The literatures concerning DMT for children and adolescents with MSwere retrieved in the Cochrane Library, MEDLINE (PubMed) and EMbase database, whose references were traced as well if necessary. Based on theinclusion and exclusion criteria, the literatures were screened. Thoseincluded literatures were further processed by quality assessment, and somedata were extracted for analysis.Results:The final number of included documents was25, including596cases.Current DMT for pediatric MS patients was divided into first-line andsecond-line therapies. The first-line therapies was composed of interferon-β(IFN-β) and glatiramer acetate (GA), while the second-line therapiesincluded natalizumab (NTZ), daclizumab (DCZ), rituximab (RTX),cyclophosphamide, mitoxantrone and fingolimod (FTY720). According tothe quality assessment, the literatures were not qualified for META analysisdue to its poor evidence grades, the lack of randomized controlled studies,and the heterogeneity between studies, although part of the data can bemerged. After IFN-β treatment,86.6%of patients showed a decline inannualized relapse rate (ARR) and87.1%of the cases displayed stable ordecreased scores in the Expanded Disability Status Scale (EDSS). Theaccording percentages in patients treated with GA, NTZ and mitoxantronewere83.3%and86.7%,89.2%and87.4%,82.6%and87.0%respectively.In the case of cyclophosphamide,RTX, DCZ and FTY720treatments, eachincluded only one literature, so that data consolidation was not performed.Acute hepatotoxicity was induced by GA in one patient, progressive multifocal leukoencephalopathy (PML) was seen in one patient using NTZ,and bladder cancer was diagnosed in one case with cyclophosphamide, andother serious adverse events were not reported. For the reason that thesample size was small and the raw data was incomplete, rigorous statisticalanalysis was not performed.Conclusions:The use of DMT in children and adolescents with MS may reduce theARR of patients and the severity of the disease, and shows a certain degreeof tolerance in this population. The first-line therapy of IFN-β as an earlyapplication in adult patients has been studied in children and adolescentsmore than other drugs. When symptoms get worse or relapse frequently afterthe first-line therapies, the second-line therapies can be considered and closemonitoring of adverse events is required. However, the current researches onDMT used in pediatric MS patients are still insufficient, and the evidenceprovided by the included literatures in this paper is poor. Therefore, in thefuture it is necessary to design large sample, multi-center, randomizedcontrolled studies to further clarify the efficacy and safety of DMT forpediatric MS patients.