Department of Neurology, New York University Grossman School of Medicine, New York, NY, USA.
Jazz Pharmaceuticals, London, United Kingdom.
Epilepsy Behav. 2024 Jul;156:109805. doi: 10.1016/j.yebeh.2024.109805. Epub 2024 Apr 26.
Dravet syndrome is a rare, early childhood-onset epileptic and developmental encephalopathy. Responses to placebo in clinical trials for epilepsy therapies range widely, but factors influencing placebo response remain poorly understood. This study explored placebo response and its effects on safety, efficacy, and quality of life outcomes in patients with Dravet syndrome.
We performed exploratory post-hoc analyses of pooled data from placebo-treated patients from the GWPCARE 1B and GWPCARE 2 randomized controlled phase III trials, comparing cannabidiol and matched placebo in 2-18 year old Dravet syndrome patients. All patients had ≥4 convulsive seizures during a baseline period of 4 weeks.
124 Dravet syndrome-treated patients were included in the analysis (2-5 years: n = 35; 6-12 years: n = 52; 13-18 years: n = 37). Convulsive seizures were experienced by all placebo group patients at all timepoints, with decreased median convulsive seizure frequency during the treatment period versus baseline; the number of convulsive seizure-free days was similar to baseline. Convulsive seizure frequency had a nominally significant positive correlation with age and a nominally significant negative correlation with body mass index. Most placebo-treated patients experienced a treatment-emergent adverse event; however, most resolved quickly, and serious adverse events were infrequent. Placebo treatment had very little effect on reported Caregiver Global Impression of Change outcomes versus baseline.
Placebo had little impact on convulsive seizure-free days and Caregiver Global Impression of Change versus baseline, suggesting that these metrics may help differentiate placebo and active treatment effects in future studies. However, future research should further assess placebo responses to confirm these results.
Dravet 综合征是一种罕见的儿童期起病的癫痫性和进行性脑病。癫痫治疗临床试验中安慰剂的反应范围很广，但影响安慰剂反应的因素仍知之甚少。本研究探讨了 Dravet 综合征患者中安慰剂反应及其对安全性、疗效和生活质量结局的影响。
我们对 GWPCARE 1B 和 GWPCARE 2 随机对照 III 期试验中安慰剂治疗患者的汇总数据进行了探索性事后分析，比较了 2-18 岁 Dravet 综合征患者中大麻二酚和匹配安慰剂的疗效。所有患者在基线期 4 周内均有≥4 次癫痫发作。
124 名 Dravet 综合征治疗患者纳入分析（2-5 岁：n=35；6-12 岁：n=52；13-18 岁：n=37）。所有安慰剂组患者在所有时间点均出现癫痫发作，治疗期间与基线相比，癫痫发作频率中位数降低；无癫痫发作天数与基线相似。癫痫发作频率与年龄呈名义上的正相关，与体重指数呈名义上的负相关。大多数安慰剂治疗患者出现治疗后不良事件；然而，大多数不良事件很快得到解决，严重不良事件很少发生。安慰剂治疗对基线时报告的照料者总体变化印象的结果影响很小。
安慰剂对无癫痫发作天数和照料者总体变化印象的影响很小，表明这些指标可能有助于在未来的研究中区分安慰剂和活性治疗的效果。然而，未来的研究应进一步评估安慰剂的反应，以证实这些结果。
