A Review of Available Treatments, Clinical Evidence, and Guidelines for Diagnosis and Treatment of Pediatric Multiple Sclerosis in the United States

Abstract

Pediatric multiple sclerosis is associated with challenges in prompt diagnosis and uncertainty regarding optimal treatment. This review aimed to identify treatment guidelines or consensus statements for pediatric patients with multiple sclerosis, US Food and Drug Administration (FDA)–approved treatment options for pediatric multiple sclerosis, and any randomized controlled trials and observational studies examining available pharmacologic treatments in the pediatric multiple sclerosis population. Literature searches were performed in MEDLINE (1946-2016), EMBASE (1974-2016), and the Cochrane Central Register of Controlled Trials to identify treatment guidelines or consensus statements, pediatric multiple sclerosis treatment approvals, and randomized controlled trials and observation studies that examine the safety and effectiveness of available disease-modifying therapies. Only 3 consensus statements provided recommendations for pharmacologic treatments for children, all 3 published before the most recent revisions of the pediatric multiple sclerosis diagnostic guidelines. Despite the changes to the clinical landscape of pediatric multiple sclerosis with the introduction of diagnostic guidelines, fingolimod is the only FDA-approved treatment for pediatric multiple sclerosis in the United States. The effectiveness and safety of other disease-modifying therapies suggested by consensus statements have been reported in relatively small prospective and retrospective observational studies. Clinical evidence from a recently completed randomized controlled trial and future global registries can inform treatment decisions for the pediatric multiple sclerosis population.

Current Advances in Pediatric Onset Multiple Sclerosis

“…At this time, fingolimod is the only FDA approved treatment for pediatric MS, but other treatments, including interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, natalizumab, rituximab, and cyclophosphamide, have been used and reports have shown the benefits of these treatments. Currently, consensus statements suggest first-line therapies as interferons or glatiramer acetate, but more recent studies have led to a discussion of the need for revision of these guidelines in light of studies showing that a large number of patients on injectable therapies require escalation of therapy [65,66]. Additionally, there is no standard definition of treatment failure across treatment centers, and with this, no guidelines for the transition of medications.…”

TyPed study: Natalizumab for the treatment of pediatric-onset multiple sclerosis in Portugal

“…Pediatric-onset MS (POMS) comprises around 5% of all MS cases (McGinley and Rossman, 2017). Current POMS therapies rely upon disease-modifying treatments (DMTs) that include the classical and injectable therapies, such as different formulations of interferon beta (IFN beta) and glatiramer acetate (GA) (Waldman et al, 2016), and some high efficacy drugs: natalizumab and fingolimod, with two more (teriflunomide and dimethyl fumarate) currently under investigation for pediatric populations (Krupp et al, 2019;Yeh and Weinstock-Guttman, 2010). Only fingolimod had specific indication to be used under 18 years of age after the publication of the PARADIGMS study.…”

Acquired Demyelinating Syndromes of the Central Nervous System in Children: The Importance of Regular Follow-up in the First Year After Onset

“…Moreover, being females, with higher age at onset, with demyelination in more than 1 central nervous system area and with oligoclonal bands in cerebrospinal fluid were predicting factors of evolution toward multiple sclerosis. 1,9 It is described that less than 10% of children with acute disseminated encephalomyelitis will experience a second demyelinating attack more than 3 months after the sentinel attack, and the majority of patients who relapse exhibit evidence of MOG antibodies. 21 Pediatric multiple sclerosis typically has a higher relapse rate in the early years after diagnosis compared with adult cohorts, and there is a shorter interval between the incident attack and a second demyelinating event.…”

“…It is recommended that all children with a first episode of acquired demyelinating syndrome excluding multiple sclerosis undergo testing for MOG antibodies; however, it does not appear to greatly improve the specificity or sensitivity of the 2017 McDonald criteria for pediatric multiple sclerosis. 8,9 In 2007, the International Paediatric Multiple Sclerosis Study Group (IPMSSG) published for the first time consensus definitions for pediatric ASD of central nervous system, with a review and an update in 2013. 10 The attempt was to unify diagnostic criteria in clinical practice, encouraging higher consistency in terminology to facilitate epidemiologic studies and thus leading to more accurate prognostic information for the families.…”

“…It is recommended that all children with a first episode of acquired demyelinating syndrome excluding multiple sclerosis undergo testing for MOG antibodies; however, it does not appear to greatly improve the specificity or sensitivity of the 2017 McDonald criteria for pediatric multiple sclerosis. 8,9…”