Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab 160062, India.
Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Seizure. 2022 Jul;99:164-175. doi: 10.1016/j.seizure.2022.04.004. Epub 2022 Apr 9.
To assess the short-term and long-term comparative efficacy and safety of ASMs for Lennox-Gastaut syndrome (LGS).
Following a systematic literature search, randomized controlled trial (RCT) and open-label extension (OLE) studies on LGS comparing ASMs with placebo or other ASMs were included. ≥50% reduction in drop seizure frequency from baseline and occurrence of treatment-emergent adverse events (TEAEs) were the primary efficacy and safety outcomes. For short-term outcomes, a network meta-analysis (NMA) reporting odds ratio (OR) with 95% confidence intervals (CIs) and hierarchy of competing interventions [surface under the cumulative ranking curve(SUCRA)] was done. Long-term outcomes were reported as proportion with 95% CIs using the random-effects model.
Fifteen studies including 1263 participants with LGS (aged 2-54years) receiving any of six ASMs [cannabidiol (CBD), clobazam (CLB), felbamate (FLB), lamotrigine (LTG), rufinamide (RFM), topiramate (TPM)] or placebo were included. High-dose CLB (1.0 mg/kg/day; CLB_H) [OR: 4.9; 95% CI: 2.3-10.8] was significantly associated with ≥50% reduction in drop seizure frequency as compared with placebo, and achieved the highest-ranking probability (0.89) based on SUCRA values (although there was an overlap between confidence intervals of effect sizes of CLB, RFM and CBD), while high-dose CBD (20 mg/kg/day; CBD_H) [OR: 3.8; 95% CI:1.6-9.0] had significantly higher odds for occurrence of any TEAEs and had the highest-ranking probability (0.85). Furthermore, the long-term treatment with CLB [78%; 95% CI: 70-85%] was associated with a significantly higher proportion of patients with reduction in drop-seizures, and long-term use of CBD [96%; 95% CI: 95-98%] was associated with a higher frequency of TEAEs.
The study findings suggest that CLB_H, CBD and RFM are the most efficacious and safest in terms of both short and long-term outcomes with CLB_H probably leading the hierarchy. Future head-to-head trials comparing these ASMs are needed.
评估抗癫痫药物（ASM）治疗 Lennox-Gastaut 综合征（LGS）的短期和长期疗效和安全性。
通过系统文献检索，纳入了比较 ASM 与安慰剂或其他 ASM 治疗 LGS 的随机对照试验（RCT）和开放标签扩展（OLE）研究。主要疗效和安全性结局为基线时癫痫发作频率减少≥50%和治疗中出现的不良事件（TEAE）的发生。对于短期结局，使用报告比值比（OR）及其 95%置信区间（CI）和竞争干预措施的分层[累积排序曲线下面积（SUCRA）]的网络荟萃分析（NMA）进行分析。使用随机效应模型，以 95%CI 报告长期结局的比例。
共纳入了 15 项研究，包括 1263 名年龄在 2-54 岁之间接受六种 ASM[大麻二酚（CBD）、氯巴占（CLB）、非氨酯（FLB）、拉莫三嗪（LTG）、鲁非酰胺（RFM）、托吡酯（TPM）]或安慰剂治疗的 LGS 患者。与安慰剂相比，高剂量 CLB（1.0mg/kg/天；CLB_H）[OR：4.9；95%CI：2.3-10.8]与癫痫发作频率减少≥50%显著相关，并且基于 SUCRA 值，获得了最高排名概率（0.89）（尽管 CLB、RFM 和 CBD 的效应大小置信区间存在重叠），而高剂量 CBD（20mg/kg/天；CBD_H）[OR：3.8；95%CI：1.6-9.0]发生任何 TEAEs 的可能性更高，且排名概率最高（0.85）。此外，CLB 的长期治疗[78%；95%CI：70-85%]与癫痫发作减少的患者比例显著增加相关，而 CBD 的长期使用[96%；95%CI：95-98%]与 TEAEs 频率增加相关。
研究结果表明，CLB_H、CBD 和 RFM 在短期和长期结果方面均最有效且最安全，CLB_H 可能处于领先地位。需要进行比较这些 ASM 的头对头试验。
