PMID- 36120377
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220920
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Efficacy and safety of adjunctive antiseizure medications for dravet syndrome: A 
      systematic review and network meta-analysis.
PG  - 980937
LID - 10.3389/fphar.2022.980937 [doi]
LID - 980937
AB  - Purpose: Recently, the U.S. Food and Drug Administration (FDA) approved 
      stiripentol, cannabidiol, and fenfluramine to treat patients with Dravet syndrome 
      (DS). Moreover, soticlestat was determined as a promising new drug for the 
      treatment of DS as it has good efficacy and safety. However, the efficacy and 
      safety of these drugs have not yet been evaluated in "head-to-head" trials. This 
      study aimed to compare and evaluate the efficacy and safety of these adjunctive 
      antiseizure medications in the treatment of DS. Methods: We searched in PubMed, 
      Embase, Cochrane Library, and Web of Science databases for randomized controlled 
      trials (RCTs) and open-label extension (OLE) studies in patients with DS. We 
      performed a random-effect meta-analysis of OLE studies and a network 
      meta-analysis for RCTs to evaluate the efficacy and safety of antiseizure 
      medications in the treatment of DS. Primary efficacy outcomes were defined as a 
      >/=50% reduction in seizure frequency compared with baseline. Furthermore, safety 
      evaluation indicators were defined as the incidence of adverse events (AEs) and 
      serious adverse events (SAEs) during treatment. Relative ranking was assessed 
      using the surface under the cumulative ranking curve (SUCRA) probabilities. 
      Results: Seven RCTs involving four antiseizure medications (stiripentol, 
      cannabidiol, fenfluramine, and soticlestat) and a total of 634 patients were 
      included in the analysis. According to the SUCRA results, all four drugs 
      significantly reduced the frequency of seizures compared with the placebo. 
      Soticlestat was the most likely to reduce seizure frequency by >/=50% compared to 
      the baseline [risk ratio (RR): 19.32; 95% confidence interval (CI): 1.20-311.40], 
      followed by stiripentol and fenfluramine. Stiripentol was ranked highest for the 
      near percentage reduction in the seizure rate from baseline [RR: 12.33; 95% CI: 
      1.71-89.17] and the occurrence of any treatment-emergent adverse events [RR: 
      3.73; 95% CI: 1.65-8.43] and serious adverse events [RR: 4.76; 95% CI: 
      0.61-37.28]. A total of ten OLE studies containing 1,121 patients were included 
      in our study. According to the results of the meta-analysis, the order of 
      probability of reducing seizure frequency by >/=50% was fenfluramine (0.715, 95% 
      CI: 0.621-0.808), stiripentol (0.604, 95% CI: 0.502-0.706), cannabidiol (0.448, 
      95% CI: 0.403-0.493). And the probability of occurrence of AEs is ranked as 
      fenfluramine(0.832, 95% CI: 0.795-0.869), cannabidiol (0.825, 95% 
      CI:0.701-0.950), stiripentol (0.823, 95% CI: 0.707-0.938), soticlestat (0.688, 
      95% CI: 0.413-0.890). Conclusion: According to the results of indirect comparison 
      of efficacy and safety, cannabidiol is slightly inferior to the other three 
      antiseizure medications in terms of efficacy and safety. Soticlestat, 
      fenfluramine, and stripentol may have little difference in efficacy, but 
      soticlestat and fenfluramine are safer. Soticlestat is probably the best 
      adjunctive antiseizure medication, followed by fenfluramine. This conclusion is 
      consistent with the comparison of long-term efficacy and safety.
CI  - Copyright (c) 2022 Wu, Zhang, Zhou, Wang, Zheng, Hu and Wu.
FAU - Wu, Jianhua
AU  - Wu J
AD  - Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, China.
FAU - Zhang, Liu
AU  - Zhang L
AD  - Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, China.
FAU - Zhou, Xi
AU  - Zhou X
AD  - Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, China.
FAU - Wang, Jiajun
AU  - Wang J
AD  - Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, China.
FAU - Zheng, Xiangyi
AU  - Zheng X
AD  - Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, China.
FAU - Hu, Hankun
AU  - Hu H
AD  - Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, China.
FAU - Wu, Dongfang
AU  - Wu D
AD  - Department of Pharmacy, Zhongnan Hospital of Wuhan University, Wuhan, China.
LA  - eng
PT  - Systematic Review
DEP - 20220831
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC9471196
OTO - NOTNLM
OT  - cannabidiol
OT  - dravet syndrome
OT  - fenfluramine
OT  - soticlestat
OT  - stiripentol
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/09/20 06:00
MHDA- 2022/09/20 06:01
PMCR- 2022/08/31
CRDT- 2022/09/19 04:39
PHST- 2022/06/29 00:00 [received]
PHST- 2022/08/05 00:00 [accepted]
PHST- 2022/09/19 04:39 [entrez]
PHST- 2022/09/20 06:00 [pubmed]
PHST- 2022/09/20 06:01 [medline]
PHST- 2022/08/31 00:00 [pmc-release]
AID - 980937 [pii]
AID - 10.3389/fphar.2022.980937 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Aug 31;13:980937. doi: 10.3389/fphar.2022.980937. 
      eCollection 2022.