What is the treatment for Multiple Sclerosis (MS) in children?

Treatment for Multiple Sclerosis in Children

The management of pediatric multiple sclerosis (MS) should follow a stepped approach using disease-modifying therapies (DMTs), with early consideration of high-efficacy DMTs rather than injectable therapies as first-line treatment due to the more aggressive nature of pediatric MS. 1

Disease Characteristics in Pediatric MS

• Pediatric MS accounts for up to 10% of all MS cases 2
• Children with MS experience:
  • Higher relapse rates than adults 3
  • Rapid MRI lesion accumulation early in disease course 3
  • Worse cognitive outcomes and physical disability long-term 3
  • Risk of developing secondary progressive MS at a younger age 3

First-Line Treatment Options

Traditional First-Line DMTs

• Injectable therapies:
  • Interferon beta (IFN-β)
  • Glatiramer acetate
• These have been the historical first-line treatments with established safety profiles in children 4
• However, approximately 1/3 of pediatric MS cases do not respond adequately to these medications 2

Current Recommended Approach

• High-efficacy DMTs should be considered as first-line treatment due to:
  • Better control of disease activity compared to injectables 5
  • Lower relapse rates (rate ratio = 0.45) 5
  • Lower rate of new/enlarging T2 lesions (HR = 0.51) 5
  • Lower rate of gadolinium-enhancing lesions (HR = 0.38) 5
  • Need to treat only 3.7 person-years with newer DMTs vs. injectables to prevent 1 relapse 5

Specific Treatment Options

High-Efficacy DMTs to Consider

• Natalizumab
• Ocrelizumab (FDA-approved for primary progressive MS in adults) 1
• Ofatumumab
• Fingolimod (has some pediatric data)
• Dimethyl fumarate

Important Considerations for Specific Medications

Fingolimod

• Special considerations for females:
  • Should be stopped 2 months before planned conception
  • Risk of severe increase in disability after discontinuation 6
• Safety established in pediatric patients 10 to <18 years of age 6
• Dosing: 0.25 mg or 0.5 mg daily 6
• Monitoring:
  • Pregnancy testing before starting treatment
  • Effective contraception during and 2 months after treatment
  • Monitor for seizures (reported in 5.6% of fingolimod-treated pediatric patients) 6

Monitoring Recommendations

• Regular assessment using Expanded Disability Status Scale (EDSS) 1
• Consider combining EDSS with Multiple Sclerosis Functional Composite (MSFC) for better sensitivity 1
• Systematic assessment of cognitive outcomes 1
• Collection of patient-reported outcomes including fatigue and quality of life measures 1
• Annual brain MRI monitoring with:
  • T2-weighted FLAIR sequences
  • T2-weighted fast/turbo spin echo sequences
  • Gadolinium-enhanced T1-weighted sequences
  • Diffusion-weighted imaging (for patients at risk of PML) 1

Treatment Algorithm

1. Diagnosis confirmation: Ensure diagnosis meets pediatric MS criteria
2. Risk assessment:
   • Evaluate disease activity (clinical relapses, MRI lesions)
   • Consider age (safety profiles differ by age)
   • Assess JCV antibody status if considering natalizumab
3. Initial treatment selection:
   • For highly active disease: Start with high-efficacy DMT
   • For moderate disease: Consider either high-efficacy DMT or traditional first-line agent
4. Monitoring response:
   • Clinical evaluation every 3-6 months
   • Annual MRI
   • Switch therapy if breakthrough disease activity occurs
5. Treatment escalation:
   • If inadequate response to first DMT, switch to a different mechanism of action
   • Consider AHSCT for cases refractory to high-efficacy DMTs 1

Special Considerations

• Complete immunizations before starting therapy when possible 1
• Avoid live vaccines during treatment 1
• Hispanic children may be more likely to experience breakthrough disease on first-line DMTs 7
• For JCV antibody-positive patients on natalizumab, monitor antibody levels every 6 months 1

Treatment Failure Management

• If breakthrough disease occurs on first-line therapy, consider:
  1. Switching between first-line DMTs (may be effective in some patients) 7
  2. Escalating to second-line therapies for those who fail first-line switches 7
  3. Consider broader immunosuppressive therapies (cyclophosphamide, mitoxantrone) in severe refractory cases 7

The aggressive nature of pediatric MS and its impact on developing brains supports early intervention with highly effective therapies rather than a traditional stepped approach starting with injectable medications.