Newer seizure drugs may ease status epilepticus burden in Dravet syndrome
Fenfluramine tied to fewer episodes, stiripentol to shorter duration
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Newer add-on anti-seizure medications may help reduce the burden of life-threatening status epilepticus in people with Dravet syndrome, a real-world study suggests. Fintepla (fenfluramine) was associated with a lower rate of status epilepticus, while Diacomit (stiripentol) was associated with shorter episodes.
Each additional newer anti-seizure medication used was also associated with a lower rate of status epilepticus, the data showed. In addition, first-line treatment with benzodiazepines effectively controlled most treated episodes.
“Early administration of [benzodiazepines], with repeat dosing if needed, is highly effective in achieving seizure control,” the researchers wrote. “Exposure to novel ASMs [anti-seizure medications] was associated with a reduced SE [status epilepticus] burden, supporting optimized long-term therapy to reduce SE frequency and severity in DS [Dravet syndrome].”
The study, “Impact of Novel Anti-Seizure Medications on Status Epilepticus in Dravet Syndrome: A Multicenter Real-World Cohort Study,” was published in Seizure: European Journal of Epilepsy.
How status epilepticus affects people with Dravet syndrome
In Dravet syndrome, abnormal electrical activity in the brain causes seizures that usually begin within the first year of life. At some point in their lives, most patients experience status epilepticus, a life-threatening medical emergency in which a seizure lasts too long or seizures occur repeatedly without the patients fully recovering between them.
“For many years, therapeutic options for DS were limited to broad-spectrum anti-seizure medications (ASMs) such as … clobazam,” a benzodiazepine sold as Onfi and generics, the researchers wrote. “Over the past two decades, however, the therapeutic landscape has been substantially transformed by the introduction of novel therapies.”
These newer treatments include Diacomit, Fintepla, and Epidiolex (cannabidiol), which have different mechanisms of action. In addition to reducing seizure frequency, add-on maintenance treatment with these agents “may improve long-term outcomes and even modify the natural course of the disease,” the researchers wrote.
However, their specific effects on status epilepticus in clinical practice remain unclear. To learn more, a team of researchers in Italy examined whether exposure to these three add-on medications was associated with how often status epilepticus occurred and with its severity, including how long episodes lasted.
They retrospectively analyzed data from 61 children and adults with a genetically confirmed Dravet diagnosis who experienced at least one episode of status epilepticus. All were followed at one of three Italian centers.
Their median age at the time of the study was 13 years, and 52.5% were males. All had experienced focal-to-bilateral or generalized tonic-clonic seizures, which typically involve muscle stiffening and loss of consciousness followed by rhythmic jerking of the arms and legs.
Together, 1,033 episodes of status epilepticus were reported. These episodes occurred at a median age of 28 months (nearly 2.5 years) and lasted a median of 10 minutes. Most (89.9%) were convulsive episodes.
A trigger was identified in 39.9% of episodes, with fever being the most common. In 22 episodes (2.1%), status epilepticus was refractory, meaning it persisted despite treatment with at least two appropriately selected and dosed medications, and lasted a median of 1 hour 15 minutes. Intensive care was needed in 42 episodes (4.1%), mainly to escalate treatment.
Benzodiazepines controlled most treated episodes
Most of the status epilepticus episodes (86.4%) were treated with at least one medication, while 13.6% resolved spontaneously without medication. Among treated episodes, most (95.8%) were controlled with first-line benzodiazepines, which slow down electrical activity in the brain. Second-line anti-seizure medications controlled 15 episodes (1.7%), while third-line anesthetics controlled 22 (2.5%).
Regarding add-on maintenance treatment, Fintepla was prescribed to 62.3% of patients, Diacomit to 52.5%, and Epidiolex to 23%.
Statistical analyses showed that Fintepla was significantly associated with an 81% lower rate of status epilepticus. Diacomit use was also associated with a lower status epilepticus rate, but this association was not statistically significant, meaning it could be due to chance.
Each additional newer anti-seizure medication used was associated with a 37% lower rate of status epilepticus.
Also, Diacomit treatment was significantly associated with shorter episodes, which lasted an estimated five minutes less on average. Each additional newer anti-seizure medication was also associated with episodes that were an estimated 3.7 minutes shorter, supporting the possibility of a “cumulative treatment effect,” the researchers wrote.
No refractory status epilepticus episodes were observed during exposure to Diacomit, Fintepla, or Epidiolex, “possibly suggesting a protective effect, although this finding is limited by the low number of events and should be interpreted cautiously,” the researchers wrote.
“Taken together, these findings emphasize the need for both rapid protocol-driven acute management and optimized long-term treatment strategies aimed at preventing SE,” the team concluded. “Such an approach may ultimately reduce neurological complications, mortality risk, and the burden of disease.”
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