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DOI: 10.1055/s-0041-1739606
Fenfluramine Treatment Improves Everyday Executive Functioning in Patients with Lennox-Gastaut Syndrome: Analysis from a Phase 3 Clinical Trial
Background/Purpose: Fenfluramine reduced frequencies of drop seizures and generalized tonic-clonic seizures in a recent Lennox-Gastaut syndrome (LGS) RCT. Purpose was to determine whether fenfluramine improves everyday executive function in a randomized clinical trial (RCT) of LGS patients.
Methods: LGS patients received placebo or fenfluramine (0.2 or 0.7 mg/kg/day) for 14 weeks. Executive function was evaluated at baseline and at week 14 for patients aged 5 to 18 years with the Behavior Rating Inventory of Executive Function (BRIEF) parent form; items were mapped to the updated BRIEF2. Clinically meaningful worsening in BRIEF2 indexes (Behavior Regulation [BRI], Emotion Regulation [ERI], Cognitive Regulation [CRI], Global Executive Composite [GEC]) from baseline to week 14 was defined exceeding a Reliable Change Index (RCI) ≥80% certainty. Clinically meaningful improvement was defined using a RCI ≥95% certainty. Active versus placebo treatment groups were compared statistically (Somers’ D).
Results: Data were analyzed for 137 patients (placebo, n = 45; fenfluramine, n = 92). Median T-scores at baseline were in the clinically elevated range (T ≥ 65) for BRI, CRI, and GEC (T = 66, 65, and 67, respectively; range: 35–90). Fenfluramine was associated with no significant worsening in any of the BRIEF2 indexes compared to placebo (p > 0.05; RCI ≥ 80%). Fenfluramine was associated with significant and clinically meaningful improvements in CRI (27 vs. 13%, p = 0.046) and GEC (25 vs. 11%; p = 0.034) versus placebo (RCI > 95%).
Conclusion: In an LGS population with a high frequency of executive function impairment at baseline, parents of approximately 25% of children treated with fenfluramine for 14 weeks observed clinically meaningful improvement in CRI and GEC.
The data were first presented at AAN 2021 Virtual Annual Meeting.
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Publikationsverlauf
Artikel online veröffentlicht:
28. Oktober 2021
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