TY - T1的突变状态对癫痫发作的影响结果复杂结节性硬化症(TSC)患者治疗EXIST-3研究(S9.008) JF -神经学乔-神经学六世- 90 - 15补充SP - S9.008盟Zuhal Yapici盟——大卫·弗朗茨盟——约翰·劳森AU -宽子Ikeda盟Tilman垫状非盟-裂缝Nabbou首页t AU -保罗Curatolo盟Petrus j . de Vries AU -丹尼斯Dlugos盟Bijoyesh Mookerjee AU -詹娜风扇盟安东尼娅Ridolfi AU -费边Herbst盟杰奎琳法国Y1 - 2018/04/10 UR - //www.ez-admanager.com/content/90/15_Supplement/S9.008.abstract N2 -目的:评价TSC基因突变对癫痫发作的影响结果TSC-associated患者难以发作。背景:EXIST-3 (NCT01713946)展示了重大和持续减少发作频率(SF)与everolimus安慰剂。数据是有限的影响在TSC突变状态和控制癫痫。设计/方法:包括TSC-associated难治性癫痫患者。在基线变异分析。18-week核心阶段后,患者可以进入扩展阶段和接收everolimus至ng / mL。从基线平均每周科幻(反应率(RR),减少≥50%)和减少百分比(PR)在旧金山召开的中值估计扩展阶段。结果:整体突变状态用于313/366的病人。其中,17.3%,63.9%,16.6%的患者有TSC1 TSC2突变,没有突变确定(敝中断)。数据截止(2016年9月2日),患者TSC1突变,RR,公关在科幻小说中值18周的30.8% (95% ci, 18.7 - -45.1; N = 52)和34.8%(95%可信区间,18.1 - -44.2;N = 52),和1年46.7% (95% ci, 31.7 - -62.1; N = 45)和47.6%(95%可信区间,25.9 - -76.3;N = 45),分别。患者TSC2突变,RR和公关在18周中位数分别为30.9% (95% ci, 24.4 - -38.0; N = 191)和32.8%(95%可信区间,26.3 - -36.4;N = 191),和1年48.2% (95% ci, 40.3 - -56.1; N = 164)和48.6%(95%可信区间,40.1 - -57.2;N = 164),分别。敝中断病人、RR和公关在18周中位数分别为25.0% (95% ci, 14.0 - -38.9; N = 52)和27.8%(95%可信区间,8.1 - -44.4;N = 52),和1年39.5% (95% ci, 25.0 - -55.6; N = 43)和42.9%(95%可信区间,29.2 - -59.6;N = 43),分别。 Median time to response was 42, 42, and 54 weeks in patients with TSC1, TSC2, and NMI, respectively. The most frequent ≥10% all grade AEs (any cause) in TSC1/TSC2/NMI groups were mouth ulceration (31.5%/28.1%/25%), stomatitis (29.6%/32.7%/30.8%), aphthous ulcer (16.7%/12.2%/1.9%), diarrhea (7.4%/13.8%/5.8%), and pyrexia (7.4%/13.3%/7.7%).Conclusions: Adjunctive everolimus treatment resulted in meaningful reductions in SF regardless of mutation status that was sustained over time with no new safety concerns. RRs were slightly lower among patients with NMI regardless of their baseline SF.Study Supported by: Novartis Pharmaceutical CorporationDisclosure: Dr. Yapici has nothing to disclose. Dr. Franz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis. Dr. Franz has received research support from Novartis. Dr. Lawson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis. Dr. Lawson has received research support from Novartis. Dr. Ikeda has nothing to disclose. Dr. Polster has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis, Desitin, UCB Pharma, Desitin, Zogenix. Dr. Nabbout has nothing to disclose. Dr. Curatolo has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai, Shire, Novartis. Dr. de Vries has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis. Dr. de Vries has received research support from Novartis. Dr Dlugos has nothing to disclose. Dr. Mookerjee has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis. Dr. Fan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis. Dr. Ridolfi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis. Dr. Herbst has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis. Dr. French has received research support from Acorda, Alexza, Eisai Medical Research, LCGH, Lundbeck, Pfizer, SK Life Sciences, Sunovion, Takeda, and UCB. ER -