目的:本研究旨在评估六种新型抗癫痫药物(ASM)辅助治疗成人局灶性癫痫患者和青少年Dravet综合征(DS)的疗效和安全性。Lennox-Gastaut综合征(LGS),或结节性硬化症(TSC)。
方法:使用PubMed进行了全面的文献检索,Medline,Embase,和Cochrane图书馆数据库从成立到2023年10月13日。我们纳入了已发表的研究,以进行系统评价和网络荟萃分析(NMA)。根据50%的反应率和脱落率以及严重不良事件(SAE)报告了疗效和安全性。结果用累积排序曲线(SUCRA)下的表面进行排序。
结果:20个符合条件的试验,包括5516名患者和21个干预措施,包括安慰剂,为分析做出了贡献。包括ASM是brivaracetam(BRV),cenobamate(CBM),大麻二酚(CBD),芬氟拉明(FFM),依维莫司(ELM),和seticlestat(SLT)。在四种不同的癫痫亚型中比较了六种新的ASM。在局灶性癫痫治疗中,BRV似乎是安全的[与安慰剂相比,风险比(RR)=0.69,95%置信区间(CI):0.25-1.91]和有效(与安慰剂相比,RR=2.18,95%CI:1.25-3.81)。在治疗局灶性癫痫时,与BRV和CBD相比,CBM300mg在50%的应答率(SUCRA91.8%)下更有效。然而,随着剂量的增加,与其他ASM相比,出现了更多的SAE(SUCRA85.6%)。CBD对LGS(SUCRA88.4)和DS(SUCRA66.2)具有良好的疗效,但是对成人局灶性癫痫的影响并不比安慰剂好[与安慰剂相比,RR=0.83(0.36-1.93)]。NMA表明,对DS进行最适当干预(SUCRA91.2%)且副作用最小(SUCRA12.5%)的可能性为FFM。与CBD相比,高暴露于ELM表明TSC的治疗更有效(SUCRA89.7%)。需要更多高质量的SLT研究来进一步评估其疗效和安全性。纳入研究的年度复发率和副作用的比较调整漏斗图显示没有明显的漏斗图不对称。
结论:该NMA表明局灶性癫痫的最有效治疗策略,DS,Lennox-Gastaut综合征,还有TSC,分别,包括CBM300毫克,FFM,CBD,和ELM。然而,上述发现需要进一步确认。
OBJECTIVE: This study aimed to evaluate the efficacy and safety of six new antiseizure medications (ASMs) for adjunctive treatment in adult patients with focal epilepsy and adolescents with Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), or tuberous sclerosis complex (TSC).
METHODS: A comprehensive literature search was performed using PubMed, Medline, Embase, and Cochrane library databases from inception to October 13, 2023. We included published studies for a systematic
review and a network meta-analysis (NMA). The efficacy and safety were reported in terms of a 50% response rate and dropout rate along with serious adverse events (SAEs). The outcomes were ranked with the surface under the cumulative ranking curve (SUCRA).
RESULTS: Twenty eligible trials with 5516 patients and 21 interventions, including placebo, contributed to the analysis. Included ASMs were brivaracetam (BRV), cenobamate (CBM), cannabidiol (CBD), fenfluramine (FFM), everolimus (ELM), and soticlestat (SLT). The six new ASMs were compared in four different epilepsy subtypes. In focal epilepsy treatment, BRV seemed to be safe [vs placebo, risk ratio (RR) = 0.69, 95 % confidence interval (CI): 0.25-1.91] and effective (vs placebo, RR = 2.18, 95 % CI: 1.25-3.81). In treating focal epilepsy, CBM 300 mg was more effective at a 50 % response rate (SUCRA 91.8 %) compared with BRV and CBD. However, with the increase in dosage, more SAEs (SUCRA 85.6 %) appeared compared with other ASMs. CBD had good efficacy on LGS (SUCRA 88.4) and DS (SUCRA 66.2), but the effect on adult focal epilepsy was not better than that of placebo [vs placebo, RR = 0.83 (0.36-1.93)]. The NMA indicated that the likelihood of the most appropriate intervention (SUCRA 91.2 %) with minimum side effects(SUCRA 12.5 %)for the DS was FFM. Compared with CBD, high exposure to ELM demonstrated a more effective treatment of TSC (SUCRA 89.7 %). More high-quality SLT studies are needed to further evaluate the efficacy and safety. The comparison-adjusted funnel plots of annualized relapse rate and side effects in the included studies revealed no significant funnel plot asymmetry.
CONCLUSIONS: This NMA indicated that the most effective treatment strategy for focal epilepsy, DS, Lennox-Gastaut syndrome, and TSC, respectively, included CBM 300 mg, FFM, CBD, and ELM. However, the aforementioned findings need further confirmation.