A Review of the New Antiepileptic Drugs for Focal-Onset Seizures in Pediatrics

Role of Extrapolation

For the Pediatric Epilepsy Academic Consortium for Extrapolation (PEACE)

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Most antiepileptic drugs (AEDs) receive regulatory approval for children years after the drug is available in adults, encouraging off-label use of the drug in children and hindering attempts to obtain quality pediatric data in controlled trials. Extrapolating adult efficacy data to pediatrics can reduce the time between approval in adults and that in children. To extrapolate efficacy from adults to children, several assumptions must be supported, such as (1) a similar disease progression and response to interventions in adults and children, and (2) similar exposure response in adults and children. The Pediatric Epilepsy Academic Consortium for Extrapolation (PEACE) addressed these assumptions in focal-onset seizures (FOS), the most common seizure type in both adults and children. PEACE reviewed the biological and clinical evidence that supported the assumptions that children with FOS have a similar disease progression and response to intervention as adults with FOS. After age 2 years, the pathophysiological underpinnings of FOS and the biological milieu in which seizures are initiated and propagated in children, seizure semiology, electroencephalographic features, etiology and AED response to FOS in children are similar to those in adults with FOS. PEACE concluded that extrapolation of efficacy data in adults to pediatrics in FOS is supported by strong scientific and clinical evidence. However, safety and pharmacokinetic (PK) data cannot be extrapolated from adults to children. Based on extrapolation, eslicarbazepine is now approved for children with FOS, down to age 4 years. Perampanel, lacosamide and brivaracetam are now undergoing PK and safety studies for the purposes of extrapolation down to age 2 or 4 years. When done in conjunction with PK and safety investigations in children, extrapolation of adult data from adults to children can reduce the time delay between approval of effective and safe AEDs in adults and approval in children.

Original languageEnglish (US)
Pages (from-to)1-16
Number of pages16
JournalPediatric Drugs
DOIs
StateAccepted/In press - Apr 3 2018

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Anticonvulsants
Seizures
Pediatrics
Epilepsy
Pharmacokinetics
Safety
Disease Progression
Off-Label Use
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pharmacology (medical)

Cite this

A Review of the New Antiepileptic Drugs for Focal-Onset Seizures in Pediatrics : Role of Extrapolation. / For the Pediatric Epilepsy Academic Consortium for Extrapolation (PEACE).

In: Pediatric Drugs, 03.04.2018, p. 1-16.

Research output: Contribution to journalArticle

For the Pediatric Epilepsy Academic Consortium for Extrapolation (PEACE). / A Review of the New Antiepileptic Drugs for Focal-Onset Seizures in Pediatrics : Role of Extrapolation. In: Pediatric Drugs. 2018 ; pp. 1-16.
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abstract = "Most antiepileptic drugs (AEDs) receive regulatory approval for children years after the drug is available in adults, encouraging off-label use of the drug in children and hindering attempts to obtain quality pediatric data in controlled trials. Extrapolating adult efficacy data to pediatrics can reduce the time between approval in adults and that in children. To extrapolate efficacy from adults to children, several assumptions must be supported, such as (1) a similar disease progression and response to interventions in adults and children, and (2) similar exposure response in adults and children. The Pediatric Epilepsy Academic Consortium for Extrapolation (PEACE) addressed these assumptions in focal-onset seizures (FOS), the most common seizure type in both adults and children. PEACE reviewed the biological and clinical evidence that supported the assumptions that children with FOS have a similar disease progression and response to intervention as adults with FOS. After age 2 years, the pathophysiological underpinnings of FOS and the biological milieu in which seizures are initiated and propagated in children, seizure semiology, electroencephalographic features, etiology and AED response to FOS in children are similar to those in adults with FOS. PEACE concluded that extrapolation of efficacy data in adults to pediatrics in FOS is supported by strong scientific and clinical evidence. However, safety and pharmacokinetic (PK) data cannot be extrapolated from adults to children. Based on extrapolation, eslicarbazepine is now approved for children with FOS, down to age 4 years. Perampanel, lacosamide and brivaracetam are now undergoing PK and safety studies for the purposes of extrapolation down to age 2 or 4 years. When done in conjunction with PK and safety investigations in children, extrapolation of adult data from adults to children can reduce the time delay between approval of effective and safe AEDs in adults and approval in children.",
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