Efficacy and tolerability of fenfluramine in patients with Dravet syndrome: A systematic review and meta-analysis.

Affiliation

Sharawat IK(1), Panda PK(2), Kasinathan A(3), Panda P(4), Dawman L(5), Joshi K(6).
Author information:
(1)Pediatric Neurology Division, Department of Pediatrics, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, 249203, India.
(2)Pediatric Neurology Division, Department of Pediatrics, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, 249203, India. Electronic address: [Email]
(3)Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, 605006, India.
(4)Department of Medicine, SCB Medical College, Cuttack, Odisha, 753007, India.
(5)Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.
(6)Department of Endocrinology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, 249203, India.

Abstract

BACKGROUND: Dravet syndrome (DS) is an infantile-onset developmental and epileptic encephalopathy syndrome with limited treatment options. We aimed to evaluate the efficacy and tolerability of fenfluramine in patients with Dravet syndrome using meta-analytical techniques. METHODS: We searched for relevant randomized controlled trials and non-randomized studies involving children with Dravet syndrome on fenfluramine therapy in MEDLINE, CENTRAL, EMBASE, Google Scholar and Web of Science database (31 July 2020). The primary outcome for the efficacy of fenfluramine was reduction in monthly convulsive seizure frequency. We carried out a random effect meta-analysis focusing on efficacy and safety variables. Only Randomized Controlled Trials (RCT) were included in the meta-analysis. The risk of bias was assessed for each study, and GRADE was used to assess the quality of evidence for each outcome. RESULTS: Of 61 publications initially screened, 12 were reviewed as full-text. Seven articles including 2 RCTs, 4 uncontrolled studies (3 prospective and one retrospective study), and one case report described responses to fenfluramine in 144 DS patients (54 % male, mean age of 8.8 years, median dose of 0.4 mg/kg/day). Fenfluramine was found to be more efficacious than placebo, in terms of mean convulsive and total seizure frequency reduction (mean difference: -45.3 % (95 % CI: -48.1 %, -42.4 %, p < 0.00001) and -39.7 % (-46.7 %, -32.7 %, p < 0.00001)). A greater proportion of patients in the fenfluramine arm achieved >25 %, >50 %, >75 % and 100 % seizure reductions (odds ratios: 6.5 (3.7, 11.5, p < 0.00001), 10.6 (5.3, 21.3, p < 0.00001), 22.7(6.9, 75.3, p < 0.00001) and 9.3(1.7, 51.4, p = 0.01) respectively). The incidence of serious adverse events was not greater in the fenfluramine groups (OR: 1.02 (0.5, 2.19, p = 0.96)). CONCLUSION: Fenfluramine appears to be a safe and efficacious antiseizure medication in patients with Dravet syndrome.