Safety Vigilance & Management Dept., Reliability & Quality Assurance Division, Meiji Seika Pharma Co., Ltd., Tokyo, Japan.
Department of Clinical Research, National Epilepsy Center, NHO Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
Epilepsy Res. 2021 Feb;170:106535. doi: 10.1016/j.eplepsyres.2020.106535. Epub 2020 Dec 31.
A post-marketing surveillance study is investigating the safety and effectiveness of stiripentol during real-world clinical use in Japanese patients with Dravet syndrome (DS).
The safety and effectiveness of stiripentol were prospectively investigated over 104 weeks in all patients with DS who were administered the drug from November 2012 through July 2019 in Japan. Patients administered stiripentol for the first time after its approval were defined as "new patients," and those who continued to take the drug after participating in domestic clinical studies were defined as "continuous-use patients." The responder rate was defined as the proportion of patients with a ≥50 % decrease in seizure episodes at the time of assessment of stiripentol effectiveness compared with the 4 weeks before starting stiripentol. Overall improvement was evaluated by the physician in charge based on the comprehensive assessment of the patient's condition after stiripentol treatment.
Of 411 patients whose information was collected, 410 patients (376 new and 34 continuous-use) were included in the safety analysis set, and 409 (376 new and 33 continuous-use) were included in the effectiveness analysis set. The median age of new patients was 7 years (range: 0.5-50 years) at the time of stiripentol initiation; 99 % of patients were taking concomitant sodium valproate and 93 % clobazam. Adverse drug reactions occurred in 70 % of new patients; the most common were somnolence (39 %) and loss of appetite (25 %). No new safety concerns due to stiripentol were observed. The responder rate in new patients was 43 % (110/257 patients) for convulsive seizures (tonic-clonic and/or clonic convulsions), 55 % (58/105 patients) for focal impaired awareness seizures, and 62 % (56/90 patients) for generalized myoclonic seizures and/or generalized atypical absence seizures. Overall improvement (after 104 weeks or at the time of drug discontinuation) was rated as marked or moderate in 160/353 of new patients (45 %).
Stiripentol is safe and effective during long-term use in patients with DS in routine clinical practice.
一项上市后监测研究正在调查司替戊醇在日本德雷维氏综合征（DS）患者真实临床应用中的安全性和有效性。
2012 年 11 月至 2019 年 7 月期间，所有首次使用司替戊醇的 DS 患者（新患者）和参加国内临床研究后继续使用司替戊醇的患者（连续使用患者）均被纳入研究。在评估司替戊醇疗效时，与开始使用司替戊醇前的 4 周相比，发作次数减少≥50%的患者比例被定义为应答率。根据患者治疗后病情的综合评估，由主管医生对整体改善情况进行评价。
在收集到的 411 名患者信息中，410 名患者（376 名新患者和 34 名连续使用患者）被纳入安全性分析集，409 名患者（376 名新患者和 33 名连续使用患者）被纳入有效性分析集。新患者开始使用司替戊醇时的中位年龄为 7 岁（范围：0.5-50 岁）；99%的患者同时服用丙戊酸钠，93%的患者服用氯巴占。70%的新患者出现药物不良反应，最常见的是嗜睡（39%）和食欲减退（25%）。未观察到与司替戊醇相关的新安全性问题。新患者的应答率为：强直阵挛性和（或）阵挛性发作的 43%（257 例患者中有 110 例），局灶性意识障碍性发作的 55%（105 例患者中有 58 例），全面性肌阵挛性发作和（或）全面性非典型失神性发作的 62%（90 例患者中有 56 例）。在 353 名新患者中，160 名（45%）被评价为明显或中度改善。
在常规临床实践中，司替戊醇在 DS 患者长期使用中是安全有效的。
