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Pediatric Drugs

, Volume 20, Issue 3, pp 249–264 | Cite as

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

  • Alexis Arzimanoglou
  • O’Neill D’Cruz
  • Douglas Nordli
  • Shlomo Shinnar
  • Gregory L. Holmes
  • For the Pediatric Epilepsy Academic Consortium for Extrapolation (PEACE)
Review Article

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.

Notes

Compliance with Ethical Standards

Funding

No financial support was received for this study.

Conflict of interest

Dr. A. Arzimanoglou occasionally serves as an advisory board member, consultant or lecturer for Eisai, GW Pharma, Shire, Takeda and UCB and has received royalties. He has also received research grants from UCB and Caixa Bank. Dr. S. Shinnar serves on two data safety monitoring boards (DSMBs) for UCB Pharma and one for Eisai. He has received personal compensation for serving on the Scientific Advisory Board for UCB, for consulting for Mallinckrod, Neurelis, Upsher-Smith and Xeris. He has received royalties for editing a book. Dr. N. D’Cruz serves as a coordinator and industry representative to the PEACE initiative; he was previously an employee at UCB and Cyberonics, and is currently an independent industry consultant. Dr. G.L. Holmes is on DSMBs for Eisai, UCB Pharma, INCYS, Zogenix and the National Heart, Lung and Blood Institute (NHLBI). Dr. D. Nordli, Jr. has received an honorarium from Eisai for consulting work and has received royalties for editing a book.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Alexis Arzimanoglou
    • 1
    • 2
  • O’Neill D’Cruz
    • 3
  • Douglas Nordli
    • 4
  • Shlomo Shinnar
    • 5
  • Gregory L. Holmes
    • 6
  • For the Pediatric Epilepsy Academic Consortium for Extrapolation (PEACE)
  1. 1.Department of Clinical Epileptology, Sleep Disorders and Functional Pediatric NeurologyUniversity Hospitals of Lyon (HCL)LyonFrance
  2. 2.Sección Epilepsia, Sueño y Neurofisiología, Servicio NeurologíaHospital Sant Joan de Déu BarcelonaBarcelonaSpain
  3. 3.Consulting and Neurological ServicesChapel HillUSA
  4. 4.Division of Pediatric Neurology, Children’s Hospital Los AngelesKeck School of Medicine of the University of Southern CaliforniaLos AngelesUSA
  5. 5.Departments of Neurology, Pediatrics and Epidemiology and Population Health, Montefiore Medical CenterAlbert Einstein College of MedicineNew YorkUSA
  6. 6.Department of Neurological Sciences, Larner College of MedicineUniversity of VermontBurlingtonUSA

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