Misra Sunita N, Jarrar Randa, Stern John M, Becker Danielle A, Carrazana Enrique, Rabinowicz Adrian L
Formerly of Clinical Development and Medical Affairs, Neurelis, Inc., San Diego, CA, USA.
Department of Neurology, Phoenix Children's Hospital, Phoenix, AZ, USA.
Neurol Ther. 2024 Feb;13(1):221-231. doi: 10.1007/s40120-023-00568-4. Epub 2024 Jan 4.
Although prompt treatment of status epilepticus is standard of care, the effect of timing of rescue therapy administration for seizure clusters in epilepsy remains unknown. Seizure clusters are a rare but clinically important condition, and benzodiazepines are the cornerstone rescue therapy for seizure clusters in epilepsy. We characterized temporal patterns from a large dataset of treated seizure clusters in the safety study of diazepam nasal spray.
This post hoc analysis used timing data of treated seizure clusters recorded by care partners and patients in seizure diaries during a 1-year safety study. Data analysis used time from seizure start to administration of diazepam.
From 4466 observations, 3225 had data meeting criteria for analysis. Overall, median times from seizure start to dose administration, dose administration to seizure termination, and total seizure duration were 2, 3, and 7 min, respectively. In seizure clusters treated in < 5 min (median 1.0 min), median time from dose to seizure termination was 2.0 min, and median total seizure duration was 4.0 min. Among seizure clusters treated in ≥ 5 min (median 10.0 min), median time to seizure termination was 10.0 min, and median total seizure duration was 23.0 min. Previously published safety results reported that over a mean participation of 1.5 years, 82.2% of patients had ≥ 1 treatment-emergent adverse events (TEAEs) irrespective of relationship to treatment, including 30.7% with serious TEAEs; 18.4% had TEAEs deemed at least possibly related to the study drug, none of which were serious. There were no events of cardiorespiratory depression.
Echoing the importance of early use of benzodiazepines in status epilepticus, the findings from this exploratory analysis of patients with refractory epilepsy and frequent seizure clusters identify a potential benefit of early diazepam nasal spray treatment leading to faster seizure resolution within the seizure cluster. Trial Registration Information: ClinicalTrials.gov identifier NCT02721069 ( https://clinicaltrials.gov/ct2/show/NCT02721069 ).
尽管癫痫持续状态的及时治疗是标准治疗方法，但癫痫发作丛集期抢救治疗给药时机的效果仍不清楚。发作丛集是一种罕见但具有临床重要性的病症，苯二氮䓬类药物是癫痫发作丛集期的基础抢救治疗药物。我们在地西泮鼻喷雾剂的安全性研究中，从大量已治疗的发作丛集数据集里对时间模式进行了特征描述。
这项事后分析使用了在一项为期1年的安全性研究中，由护理人员和患者在发作日记中记录的已治疗发作丛集的时间数据。数据分析采用从发作开始到给予地西泮的时间。
在4466次观察中，有3225次的数据符合分析标准。总体而言，从发作开始到给药、给药到发作终止以及发作总持续时间的中位数分别为2分钟、3分钟和7分钟。在发作开始后<5分钟（中位数为1.0分钟）接受治疗的发作丛集中，从给药到发作终止的中位数时间为2.0分钟，发作总持续时间的中位数为4.0分钟。在发作开始后≥ 5分钟（中位数为10. 0分钟）接受治疗的发作丛集中，发作终止的中位数时间为10.0分钟，发作总持续时间的中位数为2 3.0分钟。先前公布的安全性结果报告称，在平均参与时间为1.5年的研究中，82.2%的患者发生了≥ 1次治疗中出现的不良事件（TEAE），无论其与治疗的关系如何，其中30.7%为严重TEAE；18.4%的患者发生了被认为至少可能与研究药物相关的TEAE，其中无一为严重事件。未发生心肺抑制事件。
这项对难治性癫痫和频繁发作丛集患者的探索性分析结果呼应了苯二氮䓬类药物在癫痫持续状态中早期使用的重要性，确定了早期使用地西泮鼻喷雾剂治疗在发作丛集内导致癫痫发作更快缓解的潜在益处。试验注册信息：ClinicalTrials.gov标识符NCT02721069（https://clinicaltrials.gov/ct2/show/NCT02721069）。
