Lundbeck LLC, Deerfield, IL, United States.
University of Wisconsin, School of Pharmacy & Department of Neurology, Madison, WI, United States.
Epilepsy Behav. 2018 Jan;78:149-154. doi: 10.1016/j.yebeh.2017.10.003. Epub 2017 Dec 22.
Given the complexities managing Lennox-Gastaut syndrome (LGS)-comorbid conditions, multiple associated seizure types that tend to be refractory to treatment-dosage optimization of antiepileptic drug (AED) treatment is a challenge. In the absence of clinical trial data on optimization of AED dosage in patients with LGS, dose titration is guided by personal experience, anecdotal evidence, and specific patient factors (age, comorbid conditions and medications, seizure types, etc.). The goal of this study was to determine whether a 20% increase in adjunctive clobazam was a reasonable benchmark for improved seizure response in patients with LGS who had responded to adjunctive clobazam treatment during a 12-week lead-in trial. This was a post hoc analysis of data from a long-term, open-label extension (OLE) study, which comprised patients who completed 1 of 2 pivotal clobazam lead-in studies. During the lead-in studies, patients received either placebo or clobazam (0.25, 0.50, or 1.0mg/kg/d) (maximum 40mg/d); during OLE, patients received clobazam up to 2.0mg/kg/d (maximum 80mg/d). The post hoc analysis population comprised patients who had ≥25%, ≥50%, or ≥75% seizure reduction from baseline during lead-in clobazam treatment and ≥12months of follow-up data during OLE. Successful dosage increase (i.e., dosage optimization) was defined as ≥20% clobazam dosage increase from OLE baseline, and improved seizure control from OLE baseline (improvement in seizure responder status, or >50% reduction in total seizure frequency). Patients were stratified by responder status after lead-in treatment (OLE baseline) and by lead-in clobazam dosage received. The findings of the analysis indicated that clobazam dosage increases of ≥20% during long-term treatment improved seizure control >80% of patients with LGS who responded to clobazam during lead-in treatment. Rates of successful dosage increase during OLE were high regardless of lead-in dosage received, with the highest rate of successful dosage increase among patients who received low-dosage clobazam during lead-in. Similarly, rates of successful dose increase were high regardless of lead-in seizure responder category, with the highest rates occurring in patients with the highest (≥75%) lead-in response.
鉴于 Lennox-Gastaut 综合征 (LGS) 合并症管理的复杂性，多种相关的癫痫发作类型往往对药物剂量优化治疗反应不佳，因此抗癫痫药物 (AED) 治疗的剂量优化是一项挑战。由于缺乏关于 LGS 患者 AED 剂量优化的临床试验数据，因此剂量调整是基于个人经验、轶事证据和特定患者因素（年龄、合并症和药物、癫痫发作类型等）。本研究的目的是确定在对辅助性氯巴占治疗有反应的 LGS 患者中，辅助性氯巴占增加 20%是否是改善癫痫发作反应的合理基准，这些患者在为期 12 周的先导试验中接受了辅助性氯巴占治疗。这是一项来自长期、开放标签扩展 (OLE) 研究的事后分析，该研究纳入了完成 2 项氯巴占先导研究之一的患者。在先导研究中，患者接受安慰剂或氯巴占（0.25、0.50 或 1.0mg/kg/d）（最大剂量 40mg/d）；在 OLE 期间，患者接受氯巴占，最大剂量为 2.0mg/kg/d（最大剂量 80mg/d）。事后分析人群包括在先导期氯巴占治疗期间从基线有≥25%、≥50%或≥75%癫痫发作减少且在 OLE 期间有≥12 个月随访数据的患者。成功剂量增加（即剂量优化）定义为 OLE 基线时氯巴占剂量增加≥20%，以及 OLE 基线时癫痫发作控制改善（癫痫发作缓解状态改善，或总癫痫发作频率减少≥50%）。患者根据先导治疗后（OLE 基线）的反应状态和接受的先导氯巴占剂量进行分层。分析结果表明，在长期治疗期间，氯巴占剂量增加≥20%，改善了 80%以上对先导治疗期间氯巴占有反应的 LGS 患者的癫痫发作控制。OLE 期间成功增加剂量的比例很高，无论接受何种先导剂量，在接受低剂量氯巴占治疗的患者中，成功增加剂量的比例最高。同样，成功增加剂量的比例很高，无论先导癫痫发作反应者类别如何，最高比例发生在反应最高（≥75%）的患者中。
