Newer Disease-Modifying Therapies Show Promise in Pediatric-Onset Multiple Sclerosis

In a single-center, retrospective study, researchers evaluated the effects of treatment with nDMTs compared with iDMTs in a cohort of patients with POMS.

In patients with pediatric-onset multiple sclerosis (POMS), a reduction in the rate of attacks and of active lesions is reported most often with the use of newer disease-modifying treatments (nDMTs), according study findings published in the European Journal of Paediatric Neurology.

The current single-center, retrospective study was conducted in individuals with MS that began prior to the age of 18 years — that is, POMS — which was diagnosed according to the International Pediatric Multiple Sclerosis Study Group criteria. In most cases, POMS usually presents in the form of relapsing-remitting MS.

The immunomodulatory agents or DMTs used to prevent relapses and to treat disability in those with POMS differ from those used in patients with adult-onset MS (AOMS). In patients with POMS, the injectable DMTs (iDMTs) interferon-β (IFN-β), and glatiramer acetate (GA) are considered first-line treatments. The majority of the 13 new agents approved by the European Medicines Agency and the US Food and Drug Administration for the treatment of AOMs in the last 2 decades are being used off-label in those with POMS, with only fingolimod and teriflunomide having been approved for the treatment of children in Europe. Of the nDMTs, teriflunomide can be considered as first-line; fingolimod as second-line; and rituximab, natalizumab, ocrelizumab, and alemtuzumab as second- or third-line treatments.

In the current study, researchers sought to evaluate the effects of treatment with nDMTs compared with iDMTs in a cohort of patients with POMS. The clinical records of all patients with POMS who had received nDMTs as either escalation therapy or initial treatment and had 12 months or more of follow-up in the pediatric neurology or neurology departments of Hacettepe University Ihsan Dogramaci Children’s Hospital in Ankara, Turkey, between 2010 and 2020, were examined. Relapses were defined as neurologic symptoms that lasted for 24 hours or more.

All of the participants were divided into 2 groups: (1) Group A: patients who were started on iDMTs and later switched to nDMTs; and (2) Group B: patients who were treated with nDMTs from onset. Annualized relapse rate (ARR), presenting symptoms, recent Expanded Disability Status Scale (EDSS) lesion load, and presence of contrast-enhancing (CE) lesions on magnetic resonance imaging (MRI) scans were compared in the 2 groups.

A total of 43 patients were enrolled in the study — 33 individuals in Group A and 10 individuals in Group B. In both of the groups, the female/male ratio, age at disease onset, duration since disease onset, and duration of receiving nDMTs were similar. In Group A, the initial disease involvement was primarily brainstem and cerebellar, whereas in Group B, the initial involvement was sensorial, brainstem/cerebellar, and optic nerve.

The nDMTs used most often were fingolimod in 51.5% (17 of 33) of the participants in Group A, compared with teriflunomide in 60.0% (6 of 10) of those in Group B. The median ARR prior to treatment was 2.0 in Group A vs 1.5 in Group B (P >.05), which decreased to a median ARR of 1.0 with the use of iDMTs in Group A and to a median of 0 with the use of nDMTs in both groups (P <.001).

In Group A, the mean follow-up was 6.7±5.0 years (range, 1 to 19 years; median, 6 years), compared with a mean follow-up of 3.9±3.7 years (range, 1 to 12 years; median, 2 years) in Group B. Based on the latest follow-up information available, median EDSS scores were 1 in Group A and 0 in Group B. Further, although the ARR had increased and the lesion load on MRI went up progressively in both of the groups during the follow-up, the rate of participants with CE lesions declined in Group B.

A major limitation of the current study was the size of the series, which prevented subgroup analyses. An additional limitation was the lack of cognitive assessment and the inability to render an effective statistical comparison with Group A because of the small number of patients in Group B.

The researchers concluded that “a switch between nDMTs at some point may be anticipated in series like ours where the use of potent nDMTs such as natalizumab and ocrelizumab is rare and is expected to increase with the acquisition of more experience and modifications of regulations over time.”

Disclosure: None of the study authors has declared affiliations with biotech, pharmaceutical, and/or device companies.  


Solmaz I, Acar Ozen P, Parlak S, Tuncer A, Anlar B. Newer disease modifying treatments in pediatric onset multiple sclerosis: experience from a single center. Eur J Paediatr Neurol. Published online June 23, 2022. doi:10.1016/j.ejpn.2022.06.013