Which First-Line Treatment Is Most Effective for Pediatric-Onset MS?

The use of highly effective therapies (HETs) in pediatric-onset multiple sclerosis (MS) is associated with a sustained reduction in disease activity over 5 years, with the most significant impact observed during the first 2 years, according to study findings published in JAMA Neurology.

Researchers conducted a retrospective observational cohort study to explore the effectiveness of highly effective therapies as index treatments for pediatric-onset MS.

The primary outcome of interest was time to first relapse following treatment. Secondary outcomes included the annualized relapse rate, magnetic resonance imaging (MRI) activity, time to progression on the Expanded Disability Status Scale (EDSS), and treatment safety and tolerability.

Statistical analyses included an adapted statistical model with flexible parameters and a multivariate logic regression model. Serious adverse event (SAE) incidence was calculated as the total number of SAEs divided by the duration of follow-up.

The Observatoire Français de la Sclérose en Plaques (OFSEP) cohort comprised 36 French MS centers. Patients were eligible for the study if they were treatment-naive children with pediatric-onset MS who commenced highly or moderately effective therapy (MET) between January 2010 and December 2022 and prior to turning age 18.  

A total of 530 patients (mean age, 16; 68.7% girls) with pediatric-onset MS were included in the study, which had a media follow-up duration of 5.8 years. Of the 530 children included, 422 (79.6%) initiated METs and 108 (20.4%) initiated HETs. Compared with the METs group, the HETs group had greater relapse activity and disability at baseline. The HETs mainly consisted of natalizumab and fingolimod, while the METs primarily consisted of interferon, glatiramer acetate, and dimethyl fumarate.

Both treatment strategies had a significant impact on the first relapse rate within the initial 2 years; however, HETs had a more pronounced effect. At 5 years, the cumulative probability of a first relapse with HETs was 41.3% vs 73.1% with METs. Compared with children initiating METs, children initiating HETs demonstrated a 54% lower risk for first relapse (adjusted hazard ratio [aHR], 0.46; 95% CI, 0.31-0.67; P <.001). HETs and METs were associated with a 91.6% and 74.0% reduction in annualized relapse rates (ARRs), respectively.

Compared with the METs group, the HETs group exhibited a 66% reduction in magnetic resonance imaging (MRI) activity at 2 years (adjusted odds ratio [aOR], 0.34; 95% CI, 0.18-0.66; P =.001).

Treatment strategy had no impact on confirmed disability progression. Annual probability of confirmed disability progression increased to 7% at 5 years post-treatment initiation. Regardless of treatment, the cumulative probability of confirmed disability progression was approximately 16.1%.

Discontinuation rates of the METs group remained constant (40 withdrawals per 100 person-years) while those of the HETs group decreased for the first 2 years (7 withdrawals per 100 person-years) before increasing. At 5 years, 50.7% of children on HETs had stopped treatment and 86.1% of children taking METs had stopped treatment. Reasons for discontinuing treatment included inefficacy (HETs, 13.6% vs METs, 63.9%) and intolerance (HETs, 6.6% vs METs, 44.8%).

After switching treatment for the first time, 92 (85.2%) children in the HETs group considered a HETs strategy, while 240 (56.9%) children from the METs group continued taking the initial treatment.

Only 7 SAEs were observed in 5 out of the185 children who initiated treatment after January 1, 2017. Of these 7 SAEs, 4 occurred in the HETs group (3.41 per 100 person-years) and 3 occurred in the METs group (1.67 per 100 person-years), showing no significant difference (P =.25).

Study limitations included the observational study design, potential underestimation of treatment switch rates during certain times, challenges in uniformly defining treatment inefficacy, and missing demographic data.

“Early treatment initiation within 2 years of disease onset can dampen disability progression also in children, highlighting an optimal time window to mitigate neurological damage,” the researchers concluded.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.