Efficacy and Safety of Fenfluramine in Lennox-Gastaut Syndrome: A Systematic Review
Muhammad Qasim Qureshi1, Rutaab Kareem1, Zainab Mehdi1, Aimen Nadeem1, Zuha Majid1, Umer Hassan1, Bakhtawar Ahmad2, Muhammad Aemaz Ur Rehman3, Sadaf Iftikhar1, Abbas Khokhar4
1Department of Neurology, King Edward Medical University, 2Department of Neurology, University of Florida, 3Department of Neurology, Massachusetts General Hospital, 4Department of Oncology, Mayo Hospital, Lahore
Objective:
This systematic review aims to explore the efficacy, safety, and tolerability of fenfluramine for seizure control in patients with Lennox-Gastaut syndrome (LGS).
Background:
Fenfluramine has been recently approved as an adjunctive medication for seizure control in patients with Lennox-Gastaut syndrome (LGS). Previously, it has been used in treatment of patients with Dravet syndrome.
Design/Methods:
We conducted a systematic literature search on MEDLINE, Cochrane, and EMBASE as per guidelines of Preferred Reporting Items for Systematic Reviews (PRISMA). Two clinical trials analysing the effects of different doses of fenfluramine were included in this review.
Results:
In a double-blind phase 3 randomised control trial (RCT), participants were randomised to receive fenfluramine (0.2 or 0.7mg/kg/d) or a placebo. In another open-label clinical trial (Lagae et al.), patients were administered fenfluramine with median dose being 0.4mg/kg/d. 50% or greater reduction in seizure frequency was assessed in both trials. The responder rate in the open-label trial was 62% at 20 weeks and 66.7% at 15 months, while responder rate in the RCT was also significant in both groups (28% in the 0.2mg/kg/day group and 25% in the 0.7mg/kg/day). The median percentage reduction in seizure frequency in the open-label trial was 53% in core and 58% in extension period, while 14.2% reduction in 0.2mg/kg/d and 26.5% reduction in 0.7mg/kg/d were reported in the RCT. Adverse effects were reported in 70% of patients in the open-label trial while the RCT reported ≥1 adverse effects in 78%, 90% and 75% of the participants from 0.2mg/kg/d , 0.7mg/kg/d and placebo groups, respectively. Adverse effects commonly seen were decreased appetite, somnolence, and fatigue.
Conclusions:
Adjunctive use of fenfluramine results in significant improvement in LGS patients refractory to standardised anti-seizure therapies. The side effects reported are usually mild.