Conference Coverage
NATIONAL HARBOR, MD—Low-dose fenfluramine continues to provide clinically meaningful seizure control in a cohort of patients that has received the treatment as an add-on therapy for more than 16 years on average, according to follow-up data presented at the 2015 Child Neurology Society Annual Meeting. In addition, treatment with low doses of fenfluramine appears to be generally well tolerated, said An-Sofie Schoonjans, MD, a pediatric neurologist at Antwerp University Hospital in Belgium, and colleagues.
Fenfluramine had been used in high doses (ie, 60 mg/day or more) for weight loss, but the drug was withdrawn from the US and European markets because it was associated with cardiac valvulopathy and pulmonary hypertension. Investigators in Belgium conducted exploratory studies of fenfluramine for refractory pediatric epilepsy, however, and some patients in the studies continued taking the drug.
A retrospective analysis of 12 patients with Dravet syndrome who were treated with low doses of fenfluramine for one to 19 years found that 10 patients still were receiving the medication in 2010 and seven had been seizure-free for at least one year. Dr. Schoonjans and colleagues reported five years of additional follow-up data on the effectiveness and safety of continued long-term use of low-dose fenfluramine in the same cohort of 10 patients. Five patients were male, and the mean age was 23.5. The mean age when the patients started fenfluramine was 6.2, and the mean duration of fenfluramine treatment was 16.6 years. The average starting dose was 12 mg/day, and the current average dose was 16 mg/day.
Seven patients experienced at least two consecutive years of seizure freedom between 2010 and 2014, and nine patients averaged less than one seizure per month during the observation period. Half averaged fewer than 0.5 seizures per month.
Four patients experienced transient cardiac valve morphologic changes, and two patients had minor persistent valve morphologic changes. No clinical symptoms of cardiac valvulopathy or pulmonary hypertension were reported. “Long-term longitudinal echocardiographic assessments continue to demonstrate no clinically meaningful signs of valvulopathy or pulmonary hypertension,” said the researchers. Adverse events included anorexia (two patients), aggressive behavior (one patient), and fatigue (one patient). The adverse events were mild and did not require dose adjustment or interruption of therapy, the investigators said.
—Jake Remaly