High-Efficacy Therapies Reduce Disability Worsening in Pediatric-Onset MS

High-efficacy disease-modifying therapies (DMTs) significantly reduce the risk for disability worsening in patients with pediatric-onset relapsing-remitting multiple sclerosis (RRMS), especially among those with minimal or mild disability during treatment initiation, according to study results published in The Lancet Child and Adolescent Health.

Previous research has indicated the benefits of high-efficacy and DMTs in reducing the risk for disability worsening in pediatric-onset MS; however, limited information is available on the effect of these therapies on modifying the disability trajectory.

In a longitudinal analysis, researchers used data from international MS registries to evaluate to the course of pediatric-onset MS in young people, as well as the effect of high-efficacy therapies (HETs) on changes in natural progression of disability in this population.

Eligible participants were younger than age 18 with RRMS and a score of at least 4 on the Expanded Disability Status Scale (EDSS) within 12 months. The 5 disability states included minimal, mild, moderate, and gait impairment, with EDSS scores ranging from 0 to greater than 4, respectively, and secondary progressive MS, as confirmed by clinicians.

Primary outcome was time to change in disability state from before to after treatment initiation.

The HETs included in the study were alemtuzumab, cladribine, daclizumab, fingolimod, mitoxantrone, natalizumab, ocrelizumab, rituximab, or autologous hematopoietic stem cell transplantation.

A total of 5224 participants (70.6% women; 69.8% White; mean age at disease onset, 15.24) with pediatric-onset MS — contributing to 91,613 visits — were included in the analysis. Of these, 4570 patients (87.5%) received DMTs. Median time from first symptom to diagnosis was 2.03 years.

During a median follow-up of 5.05 years, the researchers noted 2622 transitions among 1701 participants, with the most common transition (32.8%) being from minimal to mild disability. The effect of HETs was greatest among patients with early disease with minimal disability, who were least likely to have progression into mild disability state vs those who did not receive treatment (hazard ratio [HR], 0.41; 95% CI, 0.31-0.53; P <.0001).

Compared with no treatment, low-efficacy therapy also reduced the risk for disability progression. Patients with minimal disability who received low-efficacy therapy were less likely to have progression into mild disability (HR, 0.65; 95% CI, 0.54-0.77; P <.0001). However, the researchers observed that patients who received low HET had approximately a 2-fold higher risk for disability worsening.

Duration of MS was associated with higher risk for disability worsening, as well as a lower risk for disability improvement. The male sex and older age were predictive of transition to the next disability state (HRs, 1.34 and 1.04, respectively).

Limitations of the analysis included the inaccuracies of EDSS in detecting disability; lack of data about patients’ clinical characteristics, such as body mass index (BMI) and comorbidities; and possibility of selection bias.

The researchers concluded, “Children with relapsing−remitting multiple sclerosis should be treated early with high-efficacy therapy, before developing significant neurological impairments, to better preserve their neurological capacity.”

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