From the Department of Human Neurosciences (E.C.I., A.M., C.C., P. Pulitano, C. Panzini, A.T.G., C.D.B.), Sapienza University, Rome, Italy; Department of Precision Medicine and Genomics (E.C.), Department of Medicine, Columbia University, New York, NY; Department of Neurology (J.G., C.P.B.), Odense University Hospital; Department of Clinical Research (J.G., C.P.B.), University of Southern Denmark, Odense, Denmark; Department of Neurology (R.H.C.), Hospital de Pediatría "Prof. Dr. Juan P Garrahan," Buenos Aires, Argentina; Neurological Clinic (S.L.), Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona; Neurology Unit (G.S.), Department of Translational Medicine, University of Piemonte Orientale, and Azienda Ospedaliero-Universitaria "Maggiore della Carità," Novara; Neuromuscular and Sense Organs Department (E.R.), Careggi University Hospital, Florence; Regional Epilepsy Centre (E.F.), "Bianchi-Melacrino-Morelli" Great Metropolitan Hospital, Reggio Calabria; Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro; IRCCS NEUROMED (S.C., G.D.G.), Pozzilli, Isernia; Neurology Unit (C. Pizzanelli), Department of Clinical and Experimental Medicine, University of Pisa; Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia (L.G.)," Section of Neurosciences, University of Catania; IRCCS Istituto delle Scienze Neurologiche di Bologna (V.V., B.M.); Full member of the ERN EpiCARE; DIBINEM (V.V.), University of Bologna; Humanitas Gradenigo Hospital (P. Pignatta), Turin; Institute of Neurology (F.F., A.G.), University Magna Graecia, Catanzaro, Italy; Istanbul University Istanbul Faculty of Medicine (A.Ç.A., B.B.B.), Department of Neurology, Turkey; Neurophysiopatology and Movement Disorders Clinic (A.L.), University of Messina; Department of Science of Health School of Medicine (F.F.O.), University of Catanzaro, Italy; and EMAR Medical Center (B.B.B.), Istanbul, Turkey.
Neurology. 2024 May;102(9):e209222. doi: 10.1212/WNL.0000000000209222. Epub 2024 Apr 3.
To investigate the predictors of seizure recurrence in women of childbearing age with idiopathic generalized epilepsy (IGE) who switched from valproate (VPA) to alternative antiseizure medications (ASMs) and compare the effectiveness of levetiracetam (LEV) and lamotrigine (LTG) as VPA alternatives after switch.
This multicenter retrospective study included women of childbearing age diagnosed with IGE from 16 epilepsy centers. Study outcomes included worsening or recurrence of generalized tonic-clonic seizure (GTCS) at 12 months and 24 months after the switch from VPA to an alternative ASM. The comparative effectiveness of LEV and LTG as alternative ASM following VPA discontinuation was assessed through inverse probability treatment-weighted (IPTW) Cox regression analysis.
We included 426 women with IGE, with a median (interquartile range) age at VPA switch of 24 (19-30) years and a median VPA dosage of 750 (500-1,000) mg/d. The most common reason for VPA switch was teratogenicity concern in 249 women (58.6%), and the most common ASM used in place of VPA was LEV in 197 (46.2%) cases, followed by LTG in 140 (32.9%). GTCS worsening/recurrence occurred in 105 (24.6%) and 139 (32.6%) women at 12 and 24 months, respectively. Catamenial worsening of seizures, higher VPA dosage during switch, multiple seizure types, and shorter duration of GTCS freedom before switch were independent predictors of GTCS recurrence or worsening at 12 months according to mixed multivariable logistic regression analysis. After internal-external validation through 16 independent cohorts, the model showed an area under the curve of 0.71 (95% CI 0.64-0.77). In the subgroup of 337 women who switched to LEV or LTG, IPTW Cox regression analysis showed that LEV was associated with a reduced risk of GTCS worsening or recurrence compared with LTG (adjusted hazard ratio 0.59, 95% CI 0.40-0.87, = 0.008) during the 24-month follow-up.
Our findings can have practical implications for optimizing counselling and treatment choices in women of childbearing age with IGE and may help clinicians in making informed treatment decisions in this special population of patients.
This study provides Class III evidence that for women with IGE switching from VPA, LEV was associated with a reduced risk of GTCS worsening or recurrence compared with LTG.
研究生育期特发性全面性癫痫（IGE）女性在从丙戊酸钠（VPA）转换为其他抗癫痫药物（ASM）后癫痫发作复发的预测因素，并比较左乙拉西坦（LEV）和拉莫三嗪（LTG）作为 VPA 替代药物后的疗效。
这是一项多中心回顾性研究，纳入了来自 16 个癫痫中心的生育期特发性全面性癫痫女性患者。研究结局包括 VPA 转换为替代 ASM 后 12 个月和 24 个月时全面强直阵挛性发作（GTCS）恶化或复发。通过逆概率治疗加权（IPTW）Cox 回归分析评估 LEV 和 LTG 作为 VPA 停药后替代 ASM 的比较疗效。
我们纳入了 426 例 IGE 女性患者，VPA 转换时的中位（四分位距）年龄为 24（19-30）岁，VPA 剂量的中位数为 750（500-1000）mg/d。249 例（58.6%）患者因致畸性而更换 VPA，最常用的替代 VPA 的 ASM 是 LEV，有 197 例（46.2%），其次是 LTG，有 140 例（32.9%）。12 个月和 24 个月时，分别有 105（24.6%）和 139（32.6%）例女性出现 GTCS 恶化/复发。混合多变量逻辑回归分析显示，月经性癫痫发作加重、VPA 转换时剂量较高、多种发作类型和 GTCS 无发作时间较短是 12 个月时 GTCS 复发或加重的独立预测因素。经过 16 个独立队列的内部和外部验证，该模型的曲线下面积为 0.71（95%CI 0.64-0.77）。在 337 例转换为 LEV 或 LTG 的女性亚组中，IPTW Cox 回归分析显示，与 LTG 相比，LEV 降低了 GTCS 恶化或复发的风险（调整后的危险比为 0.59，95%CI 0.40-0.87，=0.008）。
我们的研究结果可为生育期 IGE 女性的咨询和治疗选择提供实际意义，并有助于临床医生为这一特殊患者群体做出明智的治疗决策。
本研究提供 III 级证据表明，在从 VPA 转换的 IGE 女性中，与 LTG 相比，LEV 降低了 GTCS 恶化或复发的风险。
