Safety and Efficacy of Delayed-Release Dimethyl Fumarate in Pediatric Patients With Relapsing Multiple Sclerosis (FOCUS)

Pediatr Neurol. 2018 Jun:83:19-24. doi: 10.1016/j.pediatrneurol.2018.03.007. Epub 2018 Mar 22.

Abstract

Background: No therapies have been formally approved by the Food and Drug Administration for use in pediatric multiple sclerosis, a rare disease.

Objective: We evaluated the safety, efficacy, and pharmacokinetics of dimethyl fumarate in pediatric patients with multiple sclerosis.

Methods: FOCUS, a phase 2, multicenter study of patients aged 10 to 17 years with relapsing-remitting multiple sclerosis, comprised an eight-week baseline and 24-week treatment period; during treatment, patients received dimethyl fumarate (120 mg twice daily on days one to seven; 240 mg twice a day thereafter). Magnetic resonance imaging scans were obtained at week -8, day 0, week 16, and week 24. The primary end point was the change in T2 hyperintense lesion incidence from the baseline period to the final 8 weeks of treatment. Secondary end points were pharmacokinetic parameters and adverse event incidence.

Results: Twenty of 22 enrolled patients completed the study. There was a significant reduction in T2 hyperintense lesion incidence from baseline to the final eight weeks of treatment (P = 0.009). Adverse events (most commonly gastrointestinal events and flushing) and pharmacokinetic parameters were consistent with adult findings. No serious adverse events were considered dimethyl fumarate related.

Conclusions: Dimethyl fumarate treatment was associated with a reduction in magnetic resonance imaging activity in pediatric patients; pharmacokinetic and safety profiles were consistent with those in adults. Dimethyl fumarate is a potential treatment for pediatric multiple sclerosis.

Trial registration: ClinicalTrials.gov NCT02410200.

Keywords: Dimethyl fumarate; Efficacy; Pediatric; Pharmacokinetics; Relapsing-remitting multiple sclerosis; Safety.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adolescent
  • Child
  • Delayed-Action Preparations
  • Dimethyl Fumarate / administration & dosage
  • Dimethyl Fumarate / adverse effects
  • Dimethyl Fumarate / pharmacokinetics
  • Dimethyl Fumarate / pharmacology*
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / pharmacokinetics
  • Immunosuppressive Agents / pharmacology*
  • Magnetic Resonance Imaging
  • Male
  • Multiple Sclerosis, Relapsing-Remitting / diagnostic imaging*
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Outcome Assessment, Health Care*

Substances

  • Delayed-Action Preparations
  • Immunosuppressive Agents
  • Dimethyl Fumarate

Associated data

  • ClinicalTrials.gov/NCT02410200