Authors :
Presenting Author: Rima Nabbout, MD, PhD – Reference Centre for Rare Epilepsies, Necker Enfants Malades Hospital, APHP, Member of the European Reference Network (ERN) EpiCARE; Institut Imagine; Université Paris Cité
Barry Gidal, PharmD, RPh – University of Wisconsin-Madison, School of Pharmacy
Elaine Wirrell, MD – Mayo Clinic, Rochester MN, USA.
J. Helen Cross, M.B., Ch.B., PhD – University College London NIHR BRC Great Ormond Street Institute of Child Health
Joseph Sullivan, MD – Weill Institute for Neurosciences and Benioff Children’s Hospital, University of California San Francisco
Rationale:
Managing Dravet syndrome (DS) requires a comprehensive approach centered around antiseizure medications (ASMs). Due to the drug-resistant nature of the disease, polytherapy is standard practice, with most patients receiving a combination of three ASMs. The therapeutic arsenal includes non-specific first-line treatments (valproate and clobazam), specific therapies including stiripentol (STP), cannabidiol (CBD) fenfluramine (FFA), and other ASMs such as bromide, topiramate and levetiracetam. A nominal group technique was employed to develop a consensus aimed at guiding pediatric neurologists in managing treatment combinations for patients with DS, with particular emphasis on regimens including STP.
Methods:
Based on a literature review and discussions of clinical vignettes, the nominal group - composed of 5 international experts in DS - formulated 38 statements divided into six themes: i) general principles, ii) guiding physicians to empower families, iii) STP as an add-on to specific and non-specific Dravet ASMs, iv) FFA in a regimen containing STP, v) CBD in a regimen containing STP and vi) patient follow-up during treatment initiation. These statements were evaluated on a scale from 1 (completely inappropriate) to 9 (completely appropriate) by the four pediatric neurologists and the pharmacologist of the nominal group, as well as by an international panel of 56 Dravet syndrome clinicians convened during a scientific meeting in March 2025. Statements receiving ≥75% of the votes with a score of ≥7 and/or with a median score of ≥8 were considered to have strong consensus.Results:
Thirty-four of the 38 statements (79%) achieved strong consensus in both groups; for example: ” Before considering a switch or introducing a new medication, priority should be given to optimizing the dosage of an existing treatment taking into consideration efficacy and tolerability” (General principles) or: “Physicians should provide parents or caregivers with a clear plan including written information regarding medication titration, tapering, as well as guidance on monitoring seizures and adverse effects, and when and how to seek medical advice” (Guiding physicians to empower parents). One statement did not reach consensus in both groups: “When adding CBD to any base regimen of ASM including STP, a moderate reduction in overall seizures frequency is generally anticipated”. Three statements reached consensus among the nominal group experts but not among the voting clinicians. All were related to STP-based combinations.
Conclusions:
This expert consensus, developed through a nominal group technique and supported by an independent vote from international clinicians, provides a framework for all physicians managing DS to evaluate and refine their polytherapy practices with the goal of improving patient care.
Funding: Supported by Biocodex laboratory.