Highly effective treatments for pediatric onset MS linked to best outcomes at 2 years

Key takeaways:

• Risk of treatment discontinuation at 2 years was six times higher with moderately effective therapies.
• Highly effective therapies resulted in a 54% reduction in first relapse risk sustained over 5 years.

For individuals with pediatric-onset multiple sclerosis, treatment with commonly known highly effective therapies was associated with reduced relapse risk and optimal outcome within the first 2 years, researchers wrote in JAMA Neurology.

“Early treatment after [multiple sclerosis] onset has shown benefits in reducing persistent disability in children,” Nail Benallegue, MD, PhD, of the department of pediatric neurology at Angers University in France, and colleagues wrote. “A common strategy in adult MS and [pediatric onset] MS is to escalate treatment from moderately effective therapies to highly effective therapies in non-responders.”

Moderately effective therapies for MS include treatments such as azathioprine, cyclophosphamide, dimethyl fumarate, glatiramer acetate, interferon beta, methotrexate, mycophenolate mofetil and teriflunomide, while highly effective therapies include alemtuzumab, fingolimod, mitoxantrone, cladribine, natalizumab, ocrelizumab, ofatumumab and rituximab.

Benallegue and colleagues attempted to assess the real-world association of highly effective therapies as initial treatment in children with pediatric-onset MS (POMS) compared with moderately effective therapies with disease activity.

Their retrospective cohort study was conducted between January 2010 and December 2022 and after an initial yield of 3,841 participants, a total of 530 children (mean age 16.0 years; 68.7% female) from 36 MS centers in France were included. All eligible participants were treatment-naïve, with a diagnosis of relapsing-remitting POMS who received either highly effective therapies (HET) or moderately effective therapies (MET) before the age of 18 and logged at least one follow-up clinical visit.

The primary outcome for the study was time to first relapse after index treatment, with secondary outcomes including annualized relapse rate (ARR), MRI activity at 2 years, time to 6-month confirmed disability progression measured by the Expanded Disability Status Scale (EDSS), tertiary education attainment and treatment safety/tolerability.

Benallegue and colleagues utilized an adapted statistical method to model the logarithm of event rate by penalized splines of time, allowing adjustment for effects of covariates that is sensitive to nonlinearity and interactions.

According to results, both HET and MET treatment strategies were associated with a reduced risk of first relapse within the first 2 years.

HET resulted in a 54% reduction in first relapse risk (adjusted HR = 0.46; 95% CI: 0.31-0.67) sustained over 5 years, confirmed on MRI (adjusted OR = 0.34; 95% CI: 0.18-0.66) and with a better tolerability pattern than MET.

Data further showed risk of discontinuation at 2 years was six times higher with MET (HR = 5.97; 95% CI: 2.92-12.2), with lack of efficacy and intolerance the main reasons. Index treatment, however, was not associated with EDSS progression or tertiary education attainment (adjusted OR = 0.51; 95% CI: 0.24-1.1).

“Although long-term safety studies are crucial, the apparent safety of [moderately effective therapy] is marred by treatment discontinuation and lesser early effect on disease control,” Benallegue and colleagues wrote.