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Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：在Dravet综合征儿童中使用stiripentol的疗效在两个随机分组中得到证实，双盲,安慰剂对照,第三阶段研究，即STICLO法国（1996年10月至1998年8月）和STICLO意大利（1999年4月至2000年10月），但是当时数据还没有被充分利用。
方法：此事后分析使用了其他信息，特别是在开放标签扩展(OLE)月份收集的，或由看护者在个别日记中报告，评估新的结果。
结果：总体而言，纳入64例患者(安慰剂组31例，stiripentol组33人），其中34人（53.1％）为女性。患者的平均和中位年龄（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，72％的患者在stiripentol组的广泛性强直阵挛性癫痫发作（GTCS）频率降低≥50％，安慰剂组为7%(P<0.001)，与安慰剂组的3%相比，56%的患者有显著下降(≥75%)(P<0.001)，38%的人没有GTCS，但安慰剂组无（P<0.001）。stiripentol的起效迅速，从治疗的第四天开始显着。没有GTCS的连续天数的中位最长时间在替他戊醇组中为32天,而在安慰剂组中为8.5天(P<0.001)。进一步切换到第三个月OLE，在先前接受安慰剂的患者中，癫痫发作频率从基线下降了80.2%，而在那些已经服用stiripentol的患者中没有观察到疗效变化。不良事件在stiripentol组中更常见，随着更多的嗜睡发作，厌食症,和体重减轻比安慰剂组。
结论：总之，这些对STICLO数据的新分析加强了对替利坦在Dravet综合征中具有显著疗效的证据，表现出迅速的行动和持续的反应，进一步的随机后试验也证明了这一点.
方法：此事后分析使用了其他信息，特别是在开放标签扩展(OLE)月份收集的，或由看护者在个别日记中报告，评估新的结果。
结果：总体而言，纳入64例患者(安慰剂组31例，stiripentol组33人），其中34人（53.1％）为女性。患者的平均和中位年龄（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，72％的患者在stiripentol组的广泛性强直阵挛性癫痫发作（GTCS）频率降低≥50％，安慰剂组为7%(P<0.001)，与安慰剂组的3%相比，56%的患者有显著下降(≥75%)(P<0.001)，38%的人没有GTCS，但安慰剂组无（P<0.001）。stiripentol的起效迅速，从治疗的第四天开始显着。没有GTCS的连续天数的中位最长时间在替他戊醇组中为32天,而在安慰剂组中为8.5天(P<0.001)。进一步切换到第三个月OLE，在先前接受安慰剂的患者中，癫痫发作频率从基线下降了80.2%，而在那些已经服用stiripentol的患者中没有观察到疗效变化。不良事件在stiripentol组中更常见，随着更多的嗜睡发作，厌食症,和体重减轻比安慰剂组。
结论：总之，这些对STICLO数据的新分析加强了对替利坦在Dravet综合征中具有显著疗效的证据，表现出迅速的行动和持续的反应，进一步的随机后试验也证明了这一点.
