Prioritize high-efficacy DMTs for children with MS, study suggests

Children with multiple sclerosis (MS) who start on high-efficacy therapies experience fewer relapses and reduced MRI disease activity in the following years, compared with those who are treated first with moderate-efficacy therapies, according to a new study.

Rates of severe side effects are similar for both groups, but the more effective therapies also result in less treatment discontinuation, researchers found.

“These findings suggest prioritizing initial [high-efficacy treatment] in [pediatric-onset] MS, although long-term safety studies are needed,” they wrote.

The study, “Highly Effective Therapies as First-Line Treatment for Pediatric-Onset Multiple Sclerosis,” was published in JAMA Neurology.

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More than 20 DMTs approved for relapsing MS

More than 20 disease-modifying treatments (DMTs) are approved for relapsing types of multiple sclerosis. These medications, most of which work to reduce disease-driving inflammation, can be broadly divided into two categories: moderate-efficacy treatments (METs) and high-efficacy treatments (HETs).

METs are older medications that are generally less effective at controlling MS, but have more favorable safety profiles. HETs are newer therapies that are more potent but also tend to come with more serious safety risks.

In recent years, several studies have been conducted comparing the two types of treatments in adults with MS, but not much research has been done in pediatric-onset MS (POMS), a rare form of the disease that develops in childhood.

Using a national database in France, scientists compared outcomes among 530 children with POMS who started a DMT from 2010 to 2022, at a mean age of 16 years. Among them, 422 were given METs and 108 HETs. However, the proportion of patients using HETs has increased over the years, from 13% in 2010-2012 to nearly 40% in 2019-2022.

Most children in the HET group were treated with Tysabri (natalizumab) or Gilenya (fingolimod).Most patients in the MET group were on interferon-based medicines, glatiramer acetate (sold as Copaxone among others), or Tecfidera (dimethyl fumarate). Upon starting treatment, children given HETs generally had more severe disability and higher relapse rates and lesion load.

The patients were followed for a median of 5.8 years, and the researchers built statistical models to compare the risk of future relapses after starting treatment.

The apparent safety of [moderate-efficacy treatments] is marred by treatment discontinuation and lesser early effect on disease control.

Both treatment types were associated with reduction in relapses

Compared with rates prior to starting treatment, both high- and moderate-efficacy treatments were associated with a marked reduction in the average annual relapse rate, by 91.6% with HET and by 74% with MET.

Statistical models showed, over five years, the cumulative risk of relapse was 41.3% in the HET group and 73.1% in the MET group. Put another way, the relative risk of a first relapse after starting treatment was 54% lower for patients on high-efficacy therapy.

Models also showed patients on HET had 66% fewer lesions on MRI scans the two years after starting treatment. However, no significant differences were found between the HET and MET groups in disability outcomes or ability to engage in higher education.

“The findings of this cohort study suggest a sustained reduction in disease activity over 5 years associated with use of an HET as the primary strategy in POMS,” the scientists concluded.

Statistical tests also revealed notable differences in discontinuation patterns. Specifically, for HET, discontinuation was most common in the first months after starting treatment, but then discontinuation rates declined in the subsequent years. By contrast, discontinuation rates for METs were generally steady year-over-year, with patients often stopping due to inefficacy or side effects.

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Most patients on moderate-efficacy therapies eventually switched

More than half (59.3%) of patients who started on a high-efficacy treatment stayed on that treatment for the duration of the study, and most of those who discontinued their first HET switched to a different HET. By contrast, 20.4% of patients started on MET were still taking their first therapy at the end of follow-up, and most (60.9%) eventually switched to a HET within a median of 1.9 years.

“Early HET initiation was associated with optimally controlled POMS inflammatory activity, but MET posed a higher associated risk of DMT interruption and switching due to persistent disease activity and intolerance,” the researchers wrote.

Serious safety issues were infrequent, irrespective of treatment type. In total, seven serious side effects were reported: four in the HET group and three in the MET group.

Altogether, these findings suggest initiating treatment with high-efficacy medications may lead to better outcomes for patients than starting with METs. “The apparent safety of MET is marred by treatment discontinuation and lesser early effect on disease control,” the researchers wrote.

The study is limited by its observational nature, added the scientists, who stressed a need for long-term safety studies of potent high-efficacy treatments for children with MS. Of note, the researchers have financial links to pharmaceutical companies.