Use of newer disease-modifying therapies in pediatric multiple sclerosis in the US

Abstract

ObjectiveTo characterize the use and safety of newer disease-modifying therapies (DMTs) in children with multiple sclerosis (MS) and clinically isolated syndrome (CIS) treated under 18 years of age.MethodsThis is a cohort study including children with MS or CIS followed at 12 outpatient practices participating in the US Network of Pediatric MS Centers. DMT use, including duration, dose, and side effects, was analyzed. Newer DMTs were defined as agents receiving Food and Drug Administration approval or with increased use in adult MS after 2005.ResultsAs of July 2017, 1,019 pediatric patients with MS (n = 748) or CIS (n = 271) were enrolled (65% female, mean onset 13.0 ± 3.9 years, mean follow-up 3.5 ± 3.1 years, median 1.6 visits per year). Of these, 78% (n = 587) with MS and 11% (n = 31) with CIS received DMT before 18 years of age. This consisted of at least one newer DMT in 42%, including dimethyl fumarate (n = 102), natalizumab (n = 101), rituximab (n = 57), fingolimod (n = 37), daclizumab (n = 5), and teriflunomide (n = 3). Among 17%, the initial DMT prescribed was a newer agent (36 dimethyl fumarate, 30 natalizumab, 22 rituximab, 14 fingolimod, 2 teriflunomide). Over the last 10 years, the use of newer agents has increased, particularly in those ≥12 years and to lesser extent in those <12 years. The short-term side effect profiles of newer DMTs did not differ from those reported in adults.ConclusionNewer DMTs are often used in pediatric MS, and have similar short-term safety, tolerability, and side effect profiles as in adults. These findings may help inform pediatric MS management.

Real‐World Effectiveness of Initial Disease‐Modifying Therapies in Pediatric Multiple Sclerosis

“…In addition to establishing effectiveness, a priority in studying DMTs in children includes evaluating safety. 40 In a prior study of this cohort, we reported similar short- term side effects of newer DMTs to those reported in adults, 30 although these may be underestimated due to reliance on database capture without homogeneous collection of safety data during visits. In this prior study, side effects were most common with dimethyl fumarate, including gastrointestinal side effects and rash; the most common side effects on natalizumab included headache and gastrointestinal symptoms; on rituximab, the most common side effects were rash and hypotension; there was 1 case of arrhythmia on fingolimod.…”

“…In this prior study, side effects were most common with dimethyl fumarate, including gastrointestinal side effects and rash; the most common side effects on natalizumab included headache and gastrointestinal symptoms; on rituximab, the most common side effects were rash and hypotension; there was 1 case of arrhythmia on fingolimod. 30 Longer follow-up with standardized collection of safety data is required to assess DMT safety in children, such as through open-label extension studies following pediatric clinical trials. 40 Additional safety data beyond those reported recently 30 are unfortunately not available for this cohort.…”

“…Newer DMTs include oral and infusion therapies, and included therapies receiving FDA approval or with increased use in adult MS after 2005, as previously defined. 30 DMTs classified as newer include dimethyl fumarate, fingolimod, teriflunomide, natalizumab, rituximab, ocrelizumab, and alemtuzumab. DMTs were also classified by tier of therapy, including injectable (glatiramer acetate, interferon-β), oral (dimethyl fumarate, fingolimod, teriflunomide), or infusion (natalizumab, rituximab, ocrelizumab, alemtuzumab).…”

Multiple Sclerosis in Children: Current and Emerging Concepts

“…While treatment patterns may vary, practice patterns in the United States have been evolving toward the earlier use of more potent therapies earlier in the disease course. 69…”

Aktuelle Therapieempfehlungen bei multipler Sklerose im Kindes- und Jugendalter

“…Für Natalizumab und Fingolimod liegen bereits umfangreiche Erfahrungen bei Kindern und Jugendlichen vor [6,7,11,14]. Hierbei spielen der John-Cunningham-Virus-Antikörper-Index (JCV, humanes Papillomavirus 2), die Anzahl der bisherigen Tysabri-Infusionen und eine evtl.…”