Treatment of Pediatric MS

No medication currently approved for adults with relapsing-remitting MS has completed testing for pediatric MS, although several pediatric MS trials have recently been launched. Therefore, the use of disease modifying treatments (DMTs) in pediatric MS remains off-label (unapproved) in the large majority of countries, especially for children under 12 years of age.

However, clinicians need to treat children with MS in order to prevent relapses, protect the brain from new demyelinating lesions and irreversible damage, and delay the accumulation of disability – particularly since children have a higher relapse rate than adults and more significant inflammation on MRI. Also, experience in adult-onset MS suggests that DMTs are more effective if administered early in the relapsing disease course.

The current view is to classify DMTs as first- or second-line treatment, according to regulatory rules in each country. First-line medications authorized for the use in adult patients with MS include interferon beta (IFNB), glatiramer acetate (GA), teriflunomide, dimethyl fumarate (BG12), and fingolimod in North-America. Several phase 4 observational studies have evaluated the effectiveness and safety of IFNB and GA in pediatric MS, whereas comparable information is not currently available for teriflunomide, dimethyl fumarate or fingolimod, which should be used in children only within controlled clinical trials or with extreme caution in selected cases.

• IFNB: From the observational studies that have been done in children, the general conclusion is that IFNB is effective in reducing relapse rates in the majority, though about 30% of children with MS do not respond as expected and require more aggressive treatments. The most common side effects include flu-like symptoms, muscle aches, headache, injection-site reactions, elevations of liver enzymes and blood cell abnormalities. With the limited information that is available, there is no indication that IFNB negatively affects body development in children.
• GA: The clinical outcomes in two small pediatric studies were positive and no major adverse events were recorded. Some studies have included children under the age of 10 – 12 years, for whom the results and side effects were similar to that seen in older patients.

The consensus among pediatric MS experts is that the first-line medications (IFNB and GA) should be considered standard of care for all children with MS and that treatment should be started early to prevent relapses, accumulation of disability and accumulation of brain damage. Regular follow-up is also recommended to:

• Assess clinical response with regular clinical evaluations and brain MRI
• Check the tolerability/safety
• Assess blood cell count, liver function, thyroid and kidney function

Although these treatments are administered by intramuscular (directly into a muscle) or subcutaneous (under the skin) injections, they are well-tolerated by most people, and continue to have a generally favourable safety profile. The use of acetaminophen or ibuprofen before an IFNB injection or when flu-like symptoms occur can reduce their frequency and severity.
Some rare but significant side effects have recently been reported after long term use of IFNB by adults. Careful monitoring helps to ensure that these kinds of rare adverse events are discovered promptly, which is particularly important in children who are being exposed to medications during key periods of growth and body development.

Education for children and their parents at the beginning of treatment is important for setting realistic expectations for the treatment and for providing training on injection technique and strategies to manage side effects. Switching treatment if there is an inadequate or suboptimal response should be considered.

Read the IPMSSG article.

Over the past 20 years, there has been significant progress in treatments for MS. Regulatory bodies in Europe and America have approved approximately 13 treatments for use in adults. For children, there is only limited approval for beta-interferons and glatiramer acetate use for children 12 years and older by the European regulatory agency (EMA).

Availability of disease-modifying therapies (DMTs) for children and adolescents with MS varies by region, and in some regions of the world, is extremely limited. Up to 30% of children taking a beta-interferon medication or glatiramer acetate experience new disease activity (breakthrough disease) and require therapies beyond the traditional first line treatments.

Recent legislation in both the U.S. and Europe means that new treatments that might be used in children must be evaluated in clinical studies that include children. Therefore, several clinical trials in children are underway that will provide important information regarding the effectiveness and safety of newer drugs.

This review summarizes the current knowledge of breakthrough disease; the escalation approach (starting with beta-interferon or glatiramer acetate and switching to different and/or more powerful medications as needed); and the induction approach (using a very aggressive approach at the outset in an effort to control very active disease) in children with MS. The focus of the discussion is on disease course and disability outcomes in children with MS. In addition, approaches and challenges in conducting clinical trials in the pediatric population are discussed.

In 2014 The IPMSSG held an workshop “Vitamin D – To D or Not to D? “ We focused on the issue of whether one should test for vitamin D levels and, if so, how and what and when. Presentations were offered on an overview of the topic and results of an IPMSSG members’ survey conducted prior to the symposium, an argument why children with demyelination should be monitored and treated with Vitamin D as well as a response that there will be challenges in monitoring and treating children with demyelination with Vitamin D. A panel discussion followed on testing frequency, treatment approaches, and priority areas for further work.