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Early treatment of pediatric-onset relapsing-remitting multiple sclerosis (MS) with high-efficacy therapy (HET) is associated with substantially slower disability progression than treatment with low-efficacy therapies or no treatment, new research suggested.

An analysis of over 5000 people with MS onset between the ages of 15 and 24 years found the greatest benefit among those with minimal disability at HET initiation.

"Children with relapsing-remitting MS should be treated early with high-efficacy therapy, before developing significant neurological impairments, to better preserve their neurological capacity," the researchers, led by Sifat Sharman, PhD, of the Department of Medicine, University of Melbourne, Melbourne, Australia, wrote.

The study was published online on March 25 in The Lancet Child and Adolescent Health.

While research has shown that HETs slow disability progression in adults with relapsing-remitting MS, their impact on pediatric-onset MS, particularly during the early phases, is not well understood.

To address this knowledge gap, investigators evaluated the potential impact of HETs on patients with pediatric-onset MS on transitions across five disability states, ranging from minimal disability to gait impairment and secondary progressive MS.

The study included 5224 participants (71% women) from the international MSBase registry and the Italian Multiple Sclerosis and Related Disorders Register with relapsing-remitting MS with disease onset before age 18. Participants also had at least four Expanded Disability Status Scale (EDSS) scores recorded within 1-year intervals.

The primary outcome was time to change in disability state, based on EDSS scores, and clinician-diagnosed secondary progressive MS.

Investigators compared disability progression with HETs (alemtuzumab, cladribine, daclizumab, fingolimod, mitoxantrone, natalizumab, ocrelizumab, rituximab, or autologous hematopoietic stem cell transplantation) and low-efficacy therapies (dimethyl fumarate, glatiramer acetate, interferon beta, or teriflunomide) to no treatment.

'Clinically Meaningful'

HETs reduced the hazard of disability worsening across the disability states, with the largest reduction observed in participants who initiated treatment while in the minimal disability state, vs with those who received no treatment (hazard ratio [HR], 0.41; 95% CI, 0.31-0.53).

Risk for disability worsening was also lower with low-efficacy therapy than with no treatment, although the benefit was smaller than with HETs (HR, 0.65; 95% CI, 0.54-0.77).

Compared with participants treated with an HET during the minimal disability state, those treated with low-efficacy therapy had 1.59 times (HR, 0.65 vs 0.41) higher hazard of transitioning to the next (mild) disability state.

The benefit of HETs declined with increasing disability.

The findings showed a "substantial, clinically meaningful reduction in the risk of disability worsening" with the use of HET in people with pediatric-onset MS, largely before they developed disability that would "limit their capacity," the authors wrote.

"From the point of view of maximizing the effectiveness of therapy, early administration of high-efficacy therapy is a favorable approach to treatment of pediatric-onset multiple sclerosis," they concluded.

In an accompanying editorial, E. Ann Yeh, MA, MD, professor of pediatrics neurology and director of the Pediatric Multiple Sclerosis and Demyelinating Disorders Program, University of Toronto, Ontario, Canada, noted that the rarity of pediatric-onset MS — which accounts for just 5% of all MS cases — has led to a lack of information about early use of HETs.

"Sadly, despite this and several other studies showing real-life safety and effectiveness of multiple sclerosis therapies for children, approval of and access to therapies for children with multiple sclerosis is limited," Yeh wrote.

Only one therapy (fingolimod) is approved by the US Food and Drug Administration and only two (fingolimod and teriflunomide) are approved by the European Medicines Agency for children with MS, she noted.

The results of this study "speak to the need for regulatory bodies to consider real-life effectiveness studies in decision making related to drug approval," Yeh added. "We must recognize the tremendous value of this real-life knowledge as a catalyst for action that can improve outcomes in this very vulnerable population."

This study was funded by the National Health and Medical Research Council Australia, the MS Australia Postdoctoral Fellowship, and the MSBase Foundation Fellowship, a nonprofit that receives support from Merck, Biogen, Novartis, Roche, Bayer Schering, Sanofi Genzyme, and Teva Pharmaceutical Industries. Sharman received research support from the MSBase Foundation and MS Australia. The other authors' disclosures were listed on the original paper. Yeh declared no relevant financial relationships.

Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, NJ. She is a regular contributor to numerous medical publications, including Medscape Medical News and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).