Study suggests initiating highly effective therapy as primary strategy in pediatric-onset multiple sclerosis

The findings from a multicenter cohort study that included 530 children suggest that compared with moderately effective therapies (METs), initial highly effective therapies (HETs) in pediatric-onset multiple sclerosis (POMS) was linked with a lowered risk of first relapse with optimal outcome within the first two years. It was also associated with a better midterm tolerance in children and a lower rate of treatment switching.

"Those who started taking highly effective therapies had an associated 54% reduced risk of first relapse at 5 years than those taking moderately effective therapies," the researchers reported.

In pediatric-onset multiple sclerosis, moderately effective therapies have been the main treatment. Despite the expanding use of highly effective therapies, treatment strategies for POMS still lack consensus. Therefore, Nail Benallegue and colleagues from France aimed to assess the real-world association of HET as an index treatment compared with MET with disease activity.

For this purpose, they conducted a retrospective cohort study from 2010 to 2022 until the last recorded visit and the participants were followed for a median of 5.8 years. 36 French multiple sclerosis centres participated in the OFSEP cohort.

Of the total participants in OFSEP, the study included treatment-naive children with relapsing-remitting POMS who received a first HET or MET before adulthood and at least one follow-up clinical visit. All eligible participants were included in the study, and none declined to participate.

Of the 3841 children (5.2% of 74 367 total participants in OFSEP), 530 patients (mean age, 16.0 years; 68.7% female) were included in the study.

The study's primary outcome was the time to first relapse after treatment. Secondary outcomes included magnetic resonance imaging (MRI) activity, annualized relapse rate (ARR), tertiary education attainment, time to Expanded Disability Status Scale (EDSS) progression, and treatment safety/tolerability.

An adapted statistical method was used to model the logarithm of event rate by penalized splines of time, that allowed adjustments for effects of covariates sensitive to nonlinearity and interactions.

The study led to the following findings:

• In study patients, both treatment strategies were linked with a reduced risk of first relapse within the first two years.
• HET dampened disease activity with a 54% reduction in first relapse risk (adjusted hazard ratio [HR], 0.46) sustained over 5 years, confirmed on MRI activity (adjusted odds ratio [OR], 0.34), and with a better tolerability pattern than MET.
• The risk of discontinuation at 2 years was 6 times higher with MET (HR, 5.97).
• The primary reasons for treatment discontinuation were lack of efficacy and intolerance.
• Index treatment was not associated with EDSS progression or tertiary education attainment (adjusted OR, 0.51).

The apparent safety of moderately effective therapy is marred by treatment discontinuation and lesser early effects on disease control.

"These findings suggest prioritizing initial highly effective therapy in pediatric-onset multiple sclerosis, although long-term safety studies are needed," the researchers concluded.

Reference:

Benallegue N, Rollot F, Wiertlewski S, et al. Highly Effective Therapies as First-Line Treatment for Pediatric-Onset Multiple Sclerosis. JAMA Neurol. Published online February 12, 2024. doi:10.1001/jamaneurol.2023.5566