ECTRIMS 2023: Early high-efficacy treatment helps to slow disability in pediatric-onset MS
Progression risk seen as less likely if therapy started at initial disability stage
Use of high-efficacy therapies can lower the risk of disability progression in people with childhood-onset multiple sclerosis (MS), particularly if given in early disease stages when disabling symptoms are negligible.
That’s according to data shared at the 9th joint meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), held last week in Italy and online.
Sifat Sharmin, PhD, a researcher at the University of Melbourne in Australia, discussed study findings in the presentation, “Effect of high-efficacy therapy on the course of disability in paediatric-onset multiple sclerosis.”
“We have shown that disease-modifying therapies reduced the risk of disability worsening from the earliest stage of the disease in this population,” Sharmin said.
Pediatric-onset MS often treated with low-efficacy DMTs
In most people with MS, the disease first appears in adulthood. Pediatric-onset MS, abbreviated POMS, is a rare disease form whose symptoms manifest during childhood or adolescence.
Compared with adult-onset MS, people with POMS tend to experience more frequent MS relapses. But they generally are more likely to have a better recovery from relapses, with symptoms easing substantially or disappearing entirely once the relapse ends.
“Children with MS experience two to three times more relapses than adults. Although children generally recover better from relapses, the accumulation of residual disability from frequent relapses contributes to permanent disability,” Sharmin said.
Disease-modifying therapies (DMTs) work to reduce the inflammation in the brain and spinal cord that drives MS, thereby lowering the risk of relapses and disability progression.
DMTs can be broadly divided into two categories: low-efficacy DMTs, which are medicines that aren’t as good at controlling MS but are generally quite well tolerated; and high-efficacy DMTs, which are more powerful for controlling MS but also carry more serious safety risks.
In adult-onset MS, early treatment with high-efficacy DMTs has been shown to lead to better long-term disability outcomes, but it’s been unclear whether this also applies in POMS.
Despite the evidence in adults, data across the globe show that most children with MS receive low-efficacy therapies or remain untreated.
A team of researchers analyzed data covering 5,224 POMS patients who were tracked in two large databases, the international MSBase registry and the Italian MS Register. Patients’ median age at symptom onset was 16, and their median follow-up time was more than five years. About three-quarters were female.
Disability was measured using the Expanded Disability Status Scale (EDSS), and based on these scores, patients were divided into general groups of disability.
Specifically, those with EDSS scores of 1.5 or lower were labeled “negligible disability,” those with scores of 2 to 2.5 were considered to have “minimal disability,” and those with scores of 3 or 3.5 had “moderate disability.” Scores of 4 or higher on the EDSS scale reflect problems with walking, and patients with these scores were considered the most severely disabled group.
A statistical test called a Markov model was used to examine how patients’ disability changed over the years of follow-up.
“This model allowed us to examine transitions between the disability states, while accounting for several patient-specific factors, including age, sex, disease duration, and annualized relapse rate,” Sharmin said.
She noted that the most common transition was for patients to move from “negligible” to “minimal” disability.
Highly effective DMT lowers by 59% risk of progressing to minimal disability
Researchers then compared this transition among patients given no treatment or high-efficacy DMTs — such as Lemtrada (alemtuzumab), Mavenclad (cladribine), Zinbryta (daclizumab), Gilenya (fingolimod), mitoxantrone, Tysabri (natalizumab), Ocrevus (ocrelizumab), rituximab, or stem cell therapy.
Use of these high-efficacy DMTs was found to associate with a statistically significant, 59% reduction in the risk of moving from negligible to minimal disability.
The risk of moving from minimal to moderate disability also significantly reduced by 41% with high-efficacy treatment, while the risk of moving from moderate disability to gait impairment fell by 33%.
These results suggest that “the benefit of high-efficacy therapies … is the greatest in early disease with negligible disability, and reduces with increasing disability,” Sharmin said.
Treatment with low-efficacy DMTs — such as Tecfidera (dimethyl fumarate), glatiramer acetate (sold as Copaxone and as generics), interferon beta therapies, or teriflunomide (sold as Aubagio and as generics) — also was compared with no treatment in pediatric-onset patients.
Low-efficacy DMTs associated with a 35% significantly reduced risk of transitioning from negligible to minimal disability and a 41% lower risk of going from minimal disability to gait impairment, data showed. But for transitions into more severe disability stages, low-efficacy treatment did not have a statistically significant effect.
“Among patients with negligible disability, high-efficacy therapies provided an additional … reduction in the risk of disability worsening when compared with low-efficacy therapies,” Sharmin said.
Data also showed that, across patients, those with more frequent relapses and those who had been living with MS for longer were more likely to experience worsening disability, as seen by a greater risk of reaching all transitions.
“Frequent relapses and a longer disease duration increased the risk of disability worsening,” Sharmin said. “These findings underscore the critical importance of preventing relapses in order to minimize the risk of irreversible disability, which can be mitigated with early treatment, especially with high-efficacy therapies.”
This study was funded by the National Health and Medical Research Council (NHMRC) of Australia and the MSBase Foundation.
Note: The Multiple Sclerosis News Today team is providing in-depth coverage of the 9th joint ECTRIMS-ACTRIMS meeting Oct. 11–13. Go here to see the latest stories from the conference.
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