Guerrini Renzo, Chancharme Laurent, Serraz Benjamin, Chiron Catherine
Neuroscience Department, Meyer Children's Hospital IRCCS, viale Pieraccini 24, 50139, Florence, Italy.
University of Florence, Florence, Italy.
Neurol Ther. 2024 Jun;13(3):869-884. doi: 10.1007/s40120-024-00623-8. Epub 2024 May 9.
The efficacy of stiripentol in Dravet syndrome children was evidenced in two randomized, double-blind, placebo-controlled, phase 3 studies, namely STICLO France (October 1996-August 1998) and STICLO Italy (April 1999-October 2000), but data were not fully exploited at the time.
This post-hoc analysis used additional information, notably collected during the open-label extension (OLE) month, or reported by caregivers in individual diaries, to evaluate new outcomes.
Overall, 64 patients were included (31 in the placebo group, 33 in the stiripentol group) of whom 34 (53.1%) were female. Patients' mean and median (25%; 75%) age were 9.2 years (range 3.0-20.7 years) and 8.7 years (6.0; 12.1) respectively. At the end of the double-blind treatment period, 72% of the patients in the stiripentol group had a ≥ 50% decrease in generalized tonic-clonic seizure (GTCS) frequency, versus 7% in the placebo group (P < 0.001), 56% had a profound (≥ 75%) decrease versus 3% in the placebo group (P < 0.001), and 38% were free of GTCS, but none in the placebo group (P < 0.001). The onset of stiripentol efficacy was rapid, significant from the fourth day of treatment onwards. The median longest period of consecutive days with no GTCS was 32 days in the stiripentol group compared to 8.5 days in the placebo group (P < 0.001). Further to the switch to the third month OLE, an 80.2% decrease in seizure frequency from baseline was observed in patients previously receiving placebo, while no change in efficacy was observed in those already on stiripentol. Adverse events were more frequent in the stiripentol group, with significantly more episodes of somnolence, anorexia, and weight decrease than in the placebo group.
Altogether these new analyses of the STICLO data reinforce the evidence for a remarkable efficacy of stiripentol in Dravet syndrome, with a demonstrated rapid onset of action and sustained response, as also evidenced in further post-randomized trials.
在两项随机、双盲、安慰剂对照的3期研究中，即法国的STICLO研究（1996年10月 - 1998年8月）和意大利的STICLO研究（1999年4月 - 2000年10月），已证实司替戊醇对患有德雷维特综合征儿童的疗效，但当时数据未得到充分利用。
这项事后分析使用了额外信息，特别是在开放标签扩展（OLE）月期间收集的信息，或由护理人员在个人日记中报告的信息，以评估新的结果。
总体而言，纳入了64例患者（安慰剂组31例，司替戊醇组33例），其中34例（53.1%）为女性。患者的平均年龄和年龄中位数（25%；75%）分别为9.2岁（范围3.0 - 20.7岁）和8.7岁（6.0；12.1）。在双盲治疗期结束时，司替戊醇组72%的患者全身强直阵挛性发作（GTCS）频率降低≥50%，而安慰剂组为7%（P < 0.001）；56%的患者发作频率显著降低（≥75%），安慰剂组为3%（P < 0.001）；38%的患者无GTCS发作，而安慰剂组无此情况（P < 0.001）。司替戊醇疗效起效迅速，从治疗第四天起效果显著。司替戊醇组连续无GTCS发作的最长天数中位数为32天，而安慰剂组为8.5天（P < 0.001）。在转为第三个月的OLE治疗后，先前接受安慰剂治疗的患者发作频率较基线降低了80.2%，而已经使用司替戊醇治疗的患者疗效无变化。司替戊醇组不良事件更频繁，嗜睡、厌食和体重减轻发作次数明显多于安慰剂组。
总之，对STICLO数据的这些新分析进一步证实了司替戊醇对德雷维特综合征具有显著疗效，其起效迅速且反应持续，后续随机试验也证明了这一点。
