Abstracts

Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant seizures, often requiring rational polytherapy. The diversity of options, the heterogeneity of seizures, and importance of early intervention create a complex therapeutic landscape. Consensus recommendations¹ highlight valproic acid as 1^st line treatment, stiripentol (STP), fenfluramine (FFA), and/ or clobazam (CLB) as 1^st or 2^nd line and other ASMs including cannabidiol (CBD), levetiracetam (LEV) and topiramate (TPM) as 3^rd and 4^th line. Despite recommendations, there are disparities in utilization of ASMs in DS.² Recognizing these gaps, a nominal group technique was employed to develop a consensus aimed at guiding physicians in managing treatment combinations for patients with DS, with particular emphasis on polytherapy regimens that include STP.

Thirty-five statements, tailored to the US, were developed encompassing six themes: (i) general treatment principles; (ii) strategies to support and empower families; (iii) use of STP as an add-on to both specific and non-specific Dravet ASMs; (iv) use of FFA in regimens including STP; (v) use of CBD in regimens including STP; and (vi) patient follow-up during treatment initiation. These statements were submitted for anonymous online votes by 52 US pediatric/adult neurologists experienced in managing DS. Participants rated each statement using a 9-point Likert scale. Statements were considered to have reached consensus if they met either of the following predefined criteria: ≥75% of scores ≥7 and/or a median score ≥8.

To date, 21 (40.4%) providers have submitted responses. Among the preliminary results, 23/35 statements (66%) reached strong consensus, 6 statements (17%) reached good consensus, and the remaining 6 statements (17%) did not reach consensus. There was a strong consensus regarding a “notable reduction in seizure frequency and duration” when STP was added to an ASM regimen. However, no consensus was reached on several statements addressing the management of STP with other ASMs.

The preliminary results of the expert consensus on DS treatment, developed through a nominal group and validated by independent voting among US clinicians, provide a practical framework for US providers managing DS to help guide polytherapy decisions. The initial results reinforce the infrequent use of DS-specific ASMs highlighted in previous reviews.² While there was a strong consensus supporting STP’s efficacy when added to an existing ASMs, the data revealed limited provider confidence in the management of these DS-specific ASMs, including STP, underscoring the need for targeted education.