Baulac Michel, Patten Anna, Giorgi Luigi
Hospital Pitié-Salpêtrière, Paris, France.
Epilepsia. 2014 Oct;55(10):1534-43. doi: 10.1111/epi.12749. Epub 2014 Aug 8.
To investigate the long-term safety and maintenance of efficacy of monotherapy with once-daily zonisamide versus twice-daily controlled-release carbamazepine for partial seizures in adults with newly diagnosed epilepsy.
Long-term, double-blind, extension study, conducted in patients completing a phase III noninferiority trial comparing zonisamide and carbamazepine monotherapy. Patients continued their randomized treatment, with dosing adjusted according to tolerability/response (zonisamide 200-500 mg/day; carbamazepine 400-1,200 mg/day). Safety assessments included treatment-emergent adverse events (TEAEs) and clinical laboratory parameters. Efficacy assessments included retention rate and the proportion of patients remaining seizure free for ≥24 months.
Overall, 120 (87.6%) of 137 patients randomized to zonisamide and 134 (84.8%) of 158 patients randomized to carbamazepine completed the study. More than three-fourths of patients were exposed to >24 months of treatment. For zonisamide versus carbamazepine, incidences were similar for TEAEs (52.6% vs. 46.2%), serious treatment-related TEAEs (0.7% vs. 1.9%), and TEAEs leading to withdrawal (1.5% vs. 0.6%). The incidence of treatment-related TEAEs was 26.3% for zonisamide compared with 19.6% for carbamazepine, and the most frequently reported treatment-related TEAEs were decreased weight (5.1% vs. 0%), decreased appetite (3.6% vs. 0%), memory impairment (2.9% vs. 3.2%), and decreased hemoglobin level (1.5% vs. 3.2%). Most TEAEs were of mild or moderate intensity. There were no reports of Stevens-Johnson syndrome or toxic epidermal necrolysis in either group. Zonisamide was associated with small-to-moderate decreases in bicarbonate levels from baseline (mean -3.4 mm). There were no reports of metabolic acidosis. Retention rates were generally similar between treatment groups at all time points throughout the extension study. The proportion of patients remaining seizure free for ≥ 24 months was also similar for zonisamide (32.3%) and carbamazepine (35.2%).
Once-daily zonisamide monotherapy demonstrated favorable long-term safety and maintenance of efficacy in treating partial seizures in adults with newly diagnosed epilepsy. No new or unexpected safety findings emerged.
探讨对于新诊断癫痫的成年患者，每日一次服用唑尼沙胺单药治疗与每日两次服用缓释卡马西平治疗部分性发作的长期安全性及疗效维持情况。
本研究为一项长期、双盲、扩展研究，研究对象为完成了一项比较唑尼沙胺与卡马西平单药治疗的III期非劣效性试验的患者。患者继续接受随机分组的治疗，根据耐受性/反应情况调整剂量（唑尼沙胺200 - 500毫克/天；卡马西平400 - 1200毫克/天）。安全性评估包括治疗中出现的不良事件（TEAE）和临床实验室参数。疗效评估包括保留率以及癫痫发作自由≥24个月的患者比例。
总体而言，随机分配至唑尼沙胺组的137例患者中有120例（87.6%）完成了研究，随机分配至卡马西平组的158例患者中有134例（84.8%）完成了研究。超过四分之三的患者接受了超过24个月的治疗。对于唑尼沙胺和卡马西平，TEAE的发生率相似（52.6%对46.2%），严重的治疗相关TEAE发生率相似（0.7%对1.9%），导致停药的TEAE发生率相似（1.5%对0.6%）。唑尼沙胺治疗相关TEAE的发生率为26.3%，而卡马西平为19.6%，最常报告的治疗相关TEAE为体重减轻（5.1%对0%）、食欲减退（3.6%对0%）、记忆障碍（2.9%对3.2%）和血红蛋白水平降低（1.5%对3.2%）。大多数TEAE为轻度或中度。两组均未报告史蒂文斯 - 约翰逊综合征或中毒性表皮坏死松解症。唑尼沙胺与碳酸氢盐水平从基线开始出现小到中度下降相关（平均下降 - 3.4毫摩尔）。未报告代谢性酸中毒。在整个扩展研究的所有时间点，各治疗组之间的保留率总体相似。唑尼沙胺组（32.3%）和卡马西平组（35.2%）癫痫发作自由≥24个月的患者比例也相似。
每日一次的唑尼沙胺单药治疗在治疗新诊断癫痫的成年患者部分性发作方面显示出良好的长期安全性和疗效维持情况。未出现新的或意外的安全性发现。
